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Objectives: Due to disease- or therapy-associated immunosuppression, oncological patients suffer from significantly higher morbidity and mortality due to infections transmitted by respiratory pathogens such as Streptococcus pneumoniae and influenza virus. Although the German Standing Committee on Vaccination (STIKO) provides specific recommendations for vaccination against these pathogens, there is no data on vaccination rates in this high-risk population., Methods: Data from the interventional EVO study were analyzed to provide information on vaccination rates against Streptococcus pneumoniae and influenza virus in oncological patients. Numbers presented in this publication summarize baseline and follow-up data of the control group; thus, data were not influenced by the intervention., Results: Data of 370 patients were analyzed; 20.5% of patients were treated for hematological malignancies and 79.5% for solid cancer. 28.1% of patients had received vaccination against influenza and 32.2% against Streptococcus pneumoniae; for the latter only 7.3% according recommendations. While vaccination rates where even lower for patients with thoracic carcinoma (influenza 26.7% and Streptococcus pneumoniae 6.0% according to STIKO recommendations), rates in patients with multiple myeloma were remarkably higher (39.0% and 14.6%)., Conclusions: Despite strong recommendations to vaccinate and the clear clinical need to prevent infections in the vulnerable group of oncological patients, only the minority was vaccinated against Streptococcus pneumoniae or influenza, underlining the urgent need for better vaccination strategies in this high-risk population., Competing Interests: Declarations. Ethics approval: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Brandenburg Medical School as part of a broader study context (protocol code E-01–20190123, date of approval 10 April 2019). Informed consent: Informed consent was obtained from all subjects involved in the study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Characterizing strains causing noninvasive and invasive pneumococcal disease (IPD) may inform the impact of new pneumococcal conjugate vaccines (PCVs)., Methods: During 2011-2019, among children aged 6-36 months, pneumococcal serotype distribution and antibiotic nonsusceptibility of nasopharyngeal and middle ear fluid (MEF) isolates collected at onset of acute otitis media (AOM) in Rochester, New York, were compared with IPD isolates from the Active Bacterial Core surveillance (ABCs) system across 10 US sites., Results: From Rochester, 400 (nasopharyngeal) and 156 (MEF) pneumococcal isolates were collected from 259 children. From ABCs, 907 sterile-site isolates were collected from 896 children. Non-PCV serotypes 35B and 21 were more frequent among the Rochester AOM cases, while serotypes 3, 19A, 22F, 33F, 10A, and 12F contained in PCVs were more frequent among ABCs IPD cases. The proportion of antibiotic-nonsusceptible pneumococcal isolates was generally more common among IPD cases. In 2015-2019, serotype 35B emerged as the most common serotype associated with multiclass antibiotic nonsusceptibility for both the Rochester AOM and ABCs IPD cases., Conclusions: Pneumococcal isolates from children in Rochester with AOM differ in serotype distribution and antibiotic susceptibility compared to IPD cases identified through US surveillance. Non-PCV serotype 35B emerged as a common cause of AOM and IPD., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Pneumococcal carriage is associated with increased acquisition and duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among adults. While pneumococcal conjugate vaccines (PCVs) prevent carriage of vaccine-serotype pneumococci, their potential impact on coronavirus disease 2019 (COVID-19)-related outcomes remains poorly understood in populations with prevalent immunity against SARS-CoV-2., Methods: We undertook a retrospective cohort study of adults aged ≥65 years in the Kaiser Permanente Southern California healthcare system who had received ≥2 COVID-19 vaccine doses, comparing risk of SARS-CoV-2 infection between 1 January 2021 and 31 December 2022 among recipients and nonrecipients of 13-valent PCV (PCV13) employing multiple strategies to mitigate bias from differential test-seeking behavior., Results: The ajusted hazard ratio of confirmed SARS-CoV-2 infection comparing PCV13 recipients to nonrecipients was 0.92 (95% confidence interval [CI], .90-.95), corresponding to prevention of 3.9 (95% CI, 2.6-5.3) infections per 100 person-years. Following receipt of 2, 3, and ≥4 COVID-19 vaccine doses, aHRs (95% CI) were 0.85 (.81-.89), 0.94 (.90-.97), and 0.99 (.93-1.04), respectively. The aHR (95% CI) for persons who had not received COVID-19 vaccination in the preceding 6 months was 0.90 (.86-.93), versus 0.94 (.91-.98) within 6 months after COVID-19 vaccination. Similarly, aHRs (95% CI) were 0.92 (.89-.94) for persons without history of documented SARS-CoV-2 infection, versus 1.00 (.90-1.12) for persons with documented prior infection., Conclusions: Among older adults who had received ≥2 COVID-19 vaccine doses, PCV13 was associated with modest protection against SARS-CoV-2 infection. Protective effects of PCV13 were greater among individuals expected to have weaker immune protection against SARS-CoV-2 infection., Competing Interests: Potential conflicts of interest. J. A. L. discloses receipt of research grants and consulting honoraria from Pfizer and Merck, Sharp & Dohme and consulting honoraria from Seqirus and VaxCyte, all unrelated to this research. S. Y. T. reports receipt of research grants related and unrelated to this research from Pfizer. L. R. G., A. A., A. C., L. J., and B. D. G. are employees of Pfizer and may hold stocks or stock options. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Kenya introduced Synflorix™ (GlaxoSmithKline, PCV10-GSK), a 10-valent pneumococcal conjugate vaccine, in 2011, using three primary doses and, in select areas, catch-up campaigns. Surveys conducted 1-2 years post-introduction showed a stable prevalence of pneumococcal colonization, with declines in vaccine-type carriage. However, little is known about the long-term impact of PCV10-GSK in Kenya., Methods: We conducted a cross-sectional survey of pneumococcal carriage among children aged <5 years in November-December 2017 in Kibera (Nairobi informal settlement, no catch-up) and Asembo (rural western Kenya, 2-dose catch-up for children 1-4 years), using the same methods and settings as prior annual surveys from 2009 to 2013. Participants were randomly selected from an ongoing population-based surveillance platform. Nasopharyngeal swabs were frozen in skim milk-tryptone-glucose-glycerin media within 4 h and underwent culture with broth enrichment for pneumococcus. Isolates were serotyped by polymerase chain reaction and Quellung., Results: We enrolled 504 children, including 252 from each site; >90 % of participants had received 3 doses of PCV10-GSK. Pneumococcal colonization was detected in 210 (83.3 %) participants in Kibera and 149 (59.1 %) in Asembo, which was significantly lower than the prevalence observed in 2013 (92.9 % and 85.7 %, respectively). PCV10-GSK serotypes were detected in 35/252 (13.9 %) participants in Kibera and 23/252 (9.1 %) in Asembo, respectively; these prevalences were lower, but not statistically different, from vaccine-type carriage prevalences in 2013 (17.3 % and 13.3 %, respectively). In 2017 in both sites, serotypes 3, 6A, 19A, 19F, and 35B were among the most common serotypes., Conclusion: Six years post-PCV10-GSK introduction, the prevalence of pneumococcal carriage among children has decreased, and the impact of PCV10-GSK on vaccine-type carriage has plateaued. Kenya recently changed from PCV10-GSK to Pneumosil™ (Serum Institute of India), a 10-valent PCV that includes serotypes 6A and 19A; these data provide historical context for interpreting changes in vaccine-type carriage following the PCV formulation switch., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Despite current polysaccharide and conjugate vaccine use, pneumococcal diseases remain prevalent in older adults. VAX-24 is a 24-valent pneumococcal conjugate vaccine (PCV) containing eCRM, a proprietary carrier protein with non-native amino acids (para-azidomethyl-L-phenylalanine) that undergo site-specific conjugation to pneumococcal polysaccharides that have been activated with a small-molecule linker (dibenzocyclooctyne). Site-specific conjugation utilizing click chemistry enables consistent exposure of T-cell epitopes, reduction in carrier protein to pneumococcal polysaccharide ratio, and enhances manufacturing process consistency to improve PCVs by increasing serotype coverage while minimizing carrier suppression. Healthy adults aged 65 or older were randomized in a 1:1:1:1 ratio to receive a single injection of VAX-24 at 1 of 3 dose levels (1.1, 2.2, or a mixed dose of 2.2 or 4.4 mcg) or Prevnar 20® (PCV20) in a phase 2, blinded study. Primary outcome measures were solicited local and systemic events within 7 days post-vaccination, unsolicited adverse events (AEs) within 1 month, and serious AEs, medically attended AEs, or new onset of chronic disease within 6 months of vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) were measured pre-vaccination and at 1 month post-vaccination. Of 207 participants enrolled, 200 completed the trial. Safety profiles were comparable across the three VAX-24 doses and PCV20. Robust OPA and IgG immune responses were seen for all 24 serotypes. On average, immune responses to VAX-24 2.2 mcg dose were similar or higher compared to PCV20. In adults ≥ 65 years, VAX-24 had a safety profile similar to PCV20 through six months post-vaccination and induced robust OPA and IgG responses to all 24 serotypes, supporting prior data showing that site-specific conjugation allows for increased serotype coverage with similar or higher immune response vs other PCVs. The outcome of this phase 2 study further supports use of VAX-24 2.2 mcg dose in phase 3 trials. Clinicaltrials.gov: NCT05297578., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J. Wassil, M. Sisti, J. Fairman, D. Johnson, T.-S. Migone, K. Nguyen, A. Paschenko, P. Sauer, S. Iki, M.E. Hanson, J.K. Simon are employees of Vaxcyte and may own stock or hold stock options in the company. S. Bennett is a contractor employee of Vaxcyte. B. Rankin and J. Clark are clinical trial investigators involved in Vaxcyte studies., (Copyright © 2024 Vaxcyte, Inc. Published by Elsevier Ltd.. All rights reserved.)

Background: Effective strategies are needed to improve vaccine acceptance. This study sought to determine if a peer-led vaccine education intervention embedded within community medical practices increases parental acceptance of pediatric pneumococcal conjugate vaccination., Methods: From March 2022-July 2023, we conducted a randomized trial at three pediatric health practices in predominantly Hasidic Jewish neighborhoods in New York, where vaccine deferral is common. Parents of children up to 18 months due/overdue for routine pneumococcal vaccination were randomized (1:1) to receive routine care alone or routine care plus a peer educational intervention. Peer educators trained in motivational interviewing and vaccine science provided counseling at enrollment and follow-up telephone engagement in the intervention arm at day 30 and 60. Primary outcome was child's pneumococcal immunization status by allocation arm expressed as at least one dose received between enrollment and 90 days post-enrollment., Results: 144 parent-child dyads were eligible for outcome analysis. Participants in the group receiving routine care along with peer-led vaccine counseling were significantly more likely to have their child receive at least 1 vaccine dose between enrollment and 90 days compared to the group who received routine care alone (28.4 % vs 12.9 %, risk ratio [RR] 2.21, confidence interval [CI] 1.09-4.49, p = 0.022). The effect of peer education was greatest in dyads with children less than 1 year old at enrollment (34 % vs 12.7 %, RR 2.67, CI (1.22-5.86), p = 0.009)., Conclusions: Peer vaccine education can increase vaccine acceptance compared to routine care alone and may be particularly valuable in decreasing vaccination delays for younger infants. (Funded by EGL Charitable Foundation, ClinicalTrials.gov NCT05875779)., Competing Interests: Declaration of competing interest The authors have no relevant conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

BackgroundDespite widely implemented pneumococcal vaccination programmes, Streptococcus pneumoniae remains a global risk for human health. Streptococcus pneumoniae can cause invasive (IPD) or non-invasive pneumococcal disease (NIPD). Surveillance is mainly focusing on IPD, assessing the full impact of pneumococcal vaccination programmes on pneumococcal disease is challenging.AimWe aimed to prospectively investigate serotype distribution and antimicrobial resistance (AMR) of S. pneumoniae isolates from patients with NIPD and compare with data on IPD isolates and with a 2007-2008 dataset on NIPD.MethodsBetween September 2020 and April 2023, we collected isolates and patient data from patients with NIPD from 23 clinical laboratories in Belgium. Capsular typing was performed by a validated Fourier-Transform Infrared spectroscopic method, and AMR was assessed with broth microdilution, using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints.ResultsWe received S. pneumoniae isolates from 1,008 patients with lower respiratory tract infections (n = 760), otitis media (n = 190) and sinusitis (n = 58). Serotype 3 was the most prevalent serotype among the NIPD isolates. Serotypes not included in the 20-valent pneumococcal conjugate vaccine (PCV20) were significantly more common among the NIPD than among the IPD isolates. Antimicrobial resistance levels were significantly higher among the NIPD isolates (n = 539; 2020-2022) compared with the IPD isolates (n = 2,344; 2021-2022). Resistance to several β-lactam antimicrobials had increased significantly compared with 15 years before.ConclusionsThe NIPD isolates were strongly associated with non-vaccine serotypes and with increased AMR levels. This underlines the importance of continued NIPD surveillance for informed policy making on vaccination programmes.

Objective: The aim of the study is to provide a population-based evaluation of vaccination coverage to prevent respiratory complications from SARS-COV-2, influenza, and pneumococcus, among community-dwelling persons with spinal cord injury/disease., Design: This is a cross-sectional survey conducted in 2022, utilizing questionnaires administered to persons with spinal cord injury/disease living in Switzerland. Main outcomes were ever-vaccination rates for SARS-COV-2, influenza, and pneumococcus. Secondary outcomes included demographics, lesion and education levels, as well as respiratory and cardiovascular conditions. Vaccine hesitancy was additionally assessed for all three vaccines in nonvaccinated persons through questions on reasons for not getting vaccinated., Results: A total of 1158 persons participated in this survey. Overall vaccination rates were highest for SARS-COV-2 86.5% (95% CI = 84.4-88.3), followed by influenza 44.6 (41.7-47.6) and pneumococcus: 7.5% (6.0-9.3). The most prominent reasons for not being vaccinated were doubt on effectiveness (72.7%) and potential side effects (60%) for SARS-COV-2, patients did not feel at risk for influenza (57%) and insufficient information from the physician (52.4%) for pneumococcus vaccination., Conclusions: In individuals with spinal cord injury/disease, vaccination coverage is notably low for influenza and especially pneumococcus. Vaccine hesitancy varies between vaccination types and is associated with vaccine-specific reasons. These findings underscore the imperative for updated clinical vaccination guidelines, improved public health information, and targeted intervention programs for specific patient groups., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to expand protection for pneumococcal disease. It contains all 13-valent pneumococcal conjugate vaccine (PCV13) components plus conjugates for 7 additional serotypes. Our primary objective with this study was to evaluate PCV20 tolerability and safety., Methods: In this phase 3, multi-country, double-blind study, healthy infants born at ≥34 weeks' gestation were randomly assigned 2:1 to receive PCV20 or PCV13 at 2, 4, 6, and 12 to 15 months of age. Safety assessments included local reactions and systemic events within 7 days after each vaccination, adverse events (AEs) from dose 1 to 1 month after dose 3 and from dose 4 to 1 month after dose 4, and serious AEs and newly diagnosed chronic medical conditions from dose 1 through 6 months after the last dose., Results: Participants received PCV20 (N = 1000) or PCV13 (N = 504); 91.7% received all 4 doses. The frequencies of local reactions and systemic events were generally similar in PCV20 and PCV13 groups, with most reported as mild or moderate. The most common local reaction was injection site pain (PCV20, 24.7% to 40.5%; PCV13, 26.8% to 42.0%); irritability was the most common systemic event (PCV20, 54.8% to 68.2%; PCV13, 54.7% to 68.5%). AE frequencies were similar in both groups. No serious AEs were related to study vaccines. Few newly diagnosed chronic medical conditions were reported (2.8% in both groups). PCV20 was safe across multiple countries, in late preterm infants, and when administered with other vaccines., Conclusions: A 4-dose series of PCV20 had a tolerability and safety profile similar to that of PCV13.

Background: On Jan 1, 2020, the UK transitioned from a 2+1 to a 1+1 national infant immunisation schedule with the 13-valent pneumococcal conjugate vaccine (PCV13). We assessed whether the 1+1 PCV13 schedule had any impact on incidence, disease characteristics, or outcomes after invasive pneumococcal disease (IPD) in eligible children aged 0-3 years., Methods: The UK Health Security Agency conducts IPD surveillance and serotyping of invasive pneumococcal isolates via whole-genome sequencing in England. IPD was defined as identification of Streptococcus pneumoniae in a sterile site. We compared IPD incidence, demographics, clinical presentation, comorbidity prevalence, serotype distribution, and case-fatality rates (CFRs) in children from a single birth cohort eligible for the 1+1 schedule (born between Jan 1, 2020, and Dec 31, 2022) who developed IPD in the 2022-23 financial year (April to March) with children from three equivalent historical birth cohorts (born between Jan 1, 2015, and Dec 31, 2019) eligible for the 2+1 schedule who developed IPD during three respective pre-pandemic financial years: 2017-18, 2018-19, and 2019-20., Findings: There were a total of 702 IPD episodes in 697 children, including 158 (incidence 8·99 per 100 000 person-years) in the single 1+1 birth cohort and 544 (incidence 9·39 per 100 000 person-years) in the 2+1 birth cohorts, with no significant difference in the incidence of overall IPD (incidence rate ratio 0·96, 95% CI 0·80-1·14, p=0·63), PCV13-type IPD (1·21, 0·71-2·00, p=0·45), or pneumococcal meningitis (0·97, 0·66-1·40, p=0·88). Comorbidity prevalence, clinical presentation, and CFRs were also similar between the two cohorts, as was the percentage of cases in infants too young to be vaccinated (<2 months old) and infants aged 5-11 months who received one or two PCV13 priming doses, in the 1+1 and 2+1 cohorts respectively., Interpretation: After 3 years, the 1+1 schedule continues to provide direct and indirect protection against PCV13-type IPD in children, with no significant change in overall IPD incidence, serotype distribution, clinical presentation, or CFRs in children eligible for the 1+1 compared with the 2+1 schedule. Ongoing surveillance will be important to assess longer-term direct and indirect population protection., Funding: None., Competing Interests: Declaration of interests The UKHSA Immunisation and Vaccine Preventable Diseases Division (affiliated with FA, MB, Y-WC, NJA, DJL, MER, and SNL) has provided vaccine manufacturers with post-marketing surveillance reports on pneumococcal and meningococcal infections which the companies are required to submit to the UK Licensing authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. SNL performs contract research on behalf of St George's University of London and the UKHSA for pharmaceutical companies but receives no personal remuneration. The Respiratory and Vaccine Preventable Bacteria Reference Unit (affiliated with JCD, SE, and DJL) at UKHSA has received grant funding from vaccine manufacturers for investigator-led research projects on pneumococcal surveillance., (Copyright © 2024 Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Immunisation is recommended internationally to protect against pneumococcal infections in HIV-infected adults. However, vaccination schedule designs are mostly based on studies of initial rather than long-term antibody responses. This UK observational study investigated the short- and long-term antibody responses to polysaccharide and glycoconjugate pneumococcal vaccines in an adult HIV-infected cohort., Methods: We studied a subgroup of 152 of 839 participants from the AIR (Assessment of Immune Responses to Routine Immunisations in HIV-infected Adults, ISRCTN95588307) study that had received pneumococcal vaccinations and had blood samples collected pre- and post-vaccination, as well as at least annually for four subsequent calendar years. Patients received either Pneumovax-23 (PPV, N = 89) or Prevenar-13 (PCV, N = 63) as their primary vaccine, with immunity assessed by measuring IgG antibody concentrations for 12 pneumococcal polysaccharide serotypes (PnPS). The primary outcome was achieving IgG antibody concentrations above the recommended World Health Organisation (WHO) threshold of 0.35 µg/mL for at least 8/12 of the PnPS assessed (WHO ≥8/12PnPS ). Patients who did not achieve WHO ≥8/12PnPS after the primary vaccination were offered further vaccination with PCV; booster vaccinations with PCV were additionally offered to those where antibody levels subsequently fell below the WHO ≥8/12PnPS threshold., Results: Patients receiving PCV as their primary pneumococcal vaccine were significantly more likely to achieve WHO ≥8/12PnPS after a single vaccine dose than those receiving PPV (54% vs. 33%, p = 0.012). This difference persisted following booster vaccination with PCV, with cumulative rates of WHO ≥8/12PnPS in those receiving PCV vs. PPV as the primary vaccine of 88% vs. 67% and 100% vs. 85% after receiving up to one and two booster vaccinations, respectively. Where WHO ≥8/12PnPS was achieved, this persisted significantly longer in those receiving PCV as their primary vaccine compared to PPV (median: 23.5 vs. 11.1 months; p = 0.010)., Conclusions: Immunisation with PCV resulted in quantitatively greater antibody responses than immunisation with PPV in a cohort of HIV-infected UK adults. Individuals receiving PCV as their primary vaccine required fewer total pneumococcal vaccine doses to achieve WHO ≥8/12PnPS and experienced greater duration of time above this threshold than those with PPV as the primary vaccine. However, the median longevity of both vaccine responses was relatively short, which supports the use of ongoing booster doses using high-valency glycoconjugate vaccines to sustain WHO ≥8/12PnPS threshold antibody levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Pneumococcal vaccination plays a crucial role in the prevention of bacterial respiratory infections caused by Streptococcus pneumoniae. Pneumococci are responsible for diseases such as pneumonia, sinusitis and acute otitis media and can cause serious invasive infections such as meningitis and bacteraemia. Pneumococcal pneumonia leads to increased morbidity and mortality, particularly in patients with chronic lung diseases such as chronic obstructive pulmonary disease (COPD). The introduction of 13-valent conjugate vaccines (pneumococcal conjugate vaccine 13 [PCV13]) has significantly reduced the burden of disease. However, infections caused by serotypes not covered by PCV13 continue to occur. Current vaccines such as the 20-valent conjugate vaccine (PCV20) provide extended serotype coverage and have shown a robust immune response in clinical trials. The recently updated recommendations of the German Standing Committee on Vaccination (Ständige Impfkommission, STIKO) include the use of PCV20 for all indication categories in adults, which represents a simplified and more effective vaccination strategy. Future developments include vaccines with even broader serotype coverage and improved immunological properties; these are expected to further reduce the burden of pneumococcal disease. Improving vaccination uptake and increasing vaccination rates, particularly among at-risk groups, remain key objectives to protect public health in the long term., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: To characterize the institutional utilization of pneumococcal vaccination during an index hospital admission for acute cerebrospinal fluid (CSF) leakage and associated infectious and clinical outcomes., Methods: This retrospective cohort study included patients hospitalized and treated for an acute CSF leak from January 2017 to June 2022. The primary outcome evaluated the incidence of pneumococcal vaccination during the index admission in patients without prior vaccination. Secondary outcomes evaluated the incidence of meningitis, time from CSF leak identification to meningitis, and mortality within 1 year of the index admission., Results: A total of 94 patients were included. Nineteen (20.2%) patients received pneumococcal vaccination prior to admission. Of the 75 patients without prior vaccination, 4 (5.3%) patients received vaccination during the admission. Meningitis occurred in 5/94 (5.3%) patients and occurred 4-24 days from CSF leak identification. Mortality was observed in 9/94 (9.6%) patients. None of the meningitis cases were attributed to culture-positive findings of pneumococcal disease., Conclusions: The results of this study demonstrate an overall low institutional utilization of pneumococcal vaccination in patients with an acute CSF leak. Infectious and clinical outcomes reflected comparable to previous reported literature. Further evaluation into the risk-benefit relationship of vaccination omission is warranted in this patient population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Netherton syndrome (NS) is a rare, severe genetic skin disorder, currently classified as an inborn error of immunity (IEI) due to previously reported immune dysregulation. We recently reported the results of an immunological evaluation showing no evidence for a relevant B- and/or T-cell mediated immunodeficiency, but immune responses after vaccination were not evaluated in that study. Therefore, we evaluated immune responses to three vaccine platforms in adult NS patients to further investigate the presence of a clinically relevant B- and/or T-cell immunodeficiency., Methods: Vaccination responses in eight adult NS patients were assessed in a cross-sectional study performed between January and August 2022. Clinical patient data were retrospectively retrieved from electronic patient files. Immune responses to a polysaccharide Streptococcus pneumoniae vaccine (PPV23) and conjugate Haemophilus influenzae type b vaccine (ActHiB) were measured. SARS-CoV-2-specific (functional) antibody and T-cell responses following booster vaccination with an mRNA-based COVID-19 vaccine were compared to controls., Results: None of the included patients suffered from recurrent and/or severe infections that could be attributed to a B- and/or T-cell immunodeficiency. ActHiB induced immune responses were normal in 7/7 NS patients. PPV23 induced responses were absent in 1/7, diminished in 2/7, and normal in 4/7 patients. Levels of SARS-CoV-2-specific binding and neutralizing antibodies after mRNA-based COVID-19 booster vaccination in NS patients were comparable to controls. SARS-CoV-2-specific CD4 + T-cell responses were detectable in all NS patients. In contrast, SARS-CoV-2-specific CD8 + T-cell responses were detectable in only 2/6 NS patients. T-cell responses to a positive control antigen pool were comparable to controls., Conclusions: Vaccine-induced immune responses were detectable after polysaccharide, conjugate and mRNA-based vaccination in our cohort of NS patients. A spectrum of responsiveness to vaccine challenges was found, with the ranges of vaccine responses overlapping those demonstrated in healthy control populations., (© 2024. The Author(s).)

Background: Streptococcus pneumoniae is a major cause of mortality globally. The introduction of pneumococcal conjugate vaccines (PCVs) has reduced the incidence of the targeted serotypes significantly, but expansion of non-targeted serotypes, serotype replacement, and incomplete vaccine-targeting contribute to pneumococcal disease in the vaccine era. Here, we characterize the changing population genetic landscape of S. pneumoniae in Norway over a 41-year period (1982-2022)., Methods: Since 2018, all cases of invasive pneumococcal disease have undergone whole-genome sequencing (WGS) at the Norwegian Institute of Public Health. In order to characterize the changing population over time, historical isolates were re-cultured and sequenced, resulting in a historical WGS dataset. Isolates were assigned to global pneumococcal sequence clusters (GPSCs) using PathogenWatch and assigned to serotypes using in silico (SeroBA) and in vitro methods (Quellung reaction). Temporal phylogenetic analyses were performed on GPSCs of particular interest., Results: The availability of WGS data allowed us to study capsular variation at the level of individual lineages. We detect highly divergent fates for different GPSCs following the introduction of PCVs. For two out of eight major GPSCs, we identified multiple instances of serotype switching from vaccine types to non-vaccine types. Dating analyses suggest that most instances of serotype switching predated the introduction of PCVs, but expansion occurred after their introduction. Furthermore, selection for penicillin non-susceptibility was not a driving force for the changing serotype distribution within the GPSCs over time., Conclusions: PCVs have been major shapers of the Norwegian disease-causing pneumococcal population, both at the level of serotype distributions and the underlying lineage dynamics. Overall, the introduction of PCVs has reduced the incidence of invasive disease. However, some GPSCs initially dominated by vaccine types escaped the effect of vaccination through expansion of non-vaccine serotypes. Close monitoring of circulating lineages and serotypes will be key for ensuring optimal vaccination coverage going forward., (© 2024. The Author(s).)

Background: Pneumococcus is a common cause of pneumonia, meningitis, and other serious infections in children. The previous study has proved that the 13-valent pneumococcal conjugate vaccine (PCV13) has sufficient immunogenicity in children. The data on long-term persistence of immunity will help the follow-up development work of pneumococcal vaccines., Methods: Children who received the full vaccination course of the tested PCV13 in the previous clinical trial were enrolled again, and these who received other pneumococcal vaccines, or were infected with one or more serotypes of S. pneumoniae corresponding to PCV13 before enrollment were excluded. Participants were divided into four groups by age which is same as that of previous trial. The study lasted for 5 years, during which we measured pneumococcal antibodies of 13 serotypes included in PCV13 at particular points in time. Geometric mean concentrations (GMCs) and seropositive rates (the rate of IgG concentration ≥0.35 μg/mL) of antibodies against 13 serotypes were calculated., Results: For the participants aged 2 months, five years after primary vaccination, except for serotypes 3 and 4, seropositive rates were 100%. GMCs of IgG antibodies against 13 serotypes ranged from 0.733 to 15.160 μg/mL. All of the participants aged 7-11 months had the serotype-specific IgG concentration ≥0.35 μg/mL four years after primary vaccination with the exception of serotypes 3, 4, 6 A and 9 V. IgG GMCs were 0.753-11.031 μg/mL. All participants aged 12-23 months and 2-5 years old had the serotype-specific IgG concentration ≥0.35 μg/mL three or two years after primary vaccination respectively, except for serotype 3. IgG GMCs ranged from 0.815 to 13.111 μg/mL, and 0.684 to 12.282 μg/mL respectively., Conclusion: PCV13 was applied to the population aged 2 months and 7 months - 5 years old with a good immune persistence, providing more extensive evidence of long-term efficacy for that vaccine., Trial Registration: The trial was registered with ClinicalTrials.gov, number NCT06210737., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The World Health Organization (WHO) encourages countries to provide appropriate vaccinations for children, adolescents, and relevant adult populations. Childhood programme have been the focus of global investments, but recent pandemics have increasingly demonstrated the value of life course vaccination. Our objective is to compare national life course immunization programmatic maturity prior to mass COVID-19 vaccine introduction, the largest adult vaccination programme, globally. As coverage estimates (typically used to assess childhood programmes) are not available for adult vaccinations, this analysis pilots a standardized quantitative metric of programmatic maturity., Methods: Through consultation with vaccination experts, we developed a standardized approach to assess national immunization programme maturity across the life course. In accordance with expert input, five vaccines were selected to represent delivery across the life course: diphtheria tetanus toxoid and pertussis (DTP); measles (MCV) second dose; human papillomavirus (HPV) final dose; pneumococcal conjugate (PCV) final dose; and seasonal influenza annual dose. Experts recommended inclusion of the following indicators for each vaccine: a legal mandate (national policy), experience delivering the vaccine (programme duration), and vaccine use (uptake for relevant populations). We developed a metric accordingly that provides up to 5 points per vaccine ("vaccine specific maturity score") which when summed forms the "life course maturity score", with a maximum score of 25. We analysed the prevalence of national policies, experience, and use by region and World Bank income group., Results: More than 55% of the 194 WHO Member States had childhood vaccine policies for all three of the vaccines considered (DTP, MCV, and PCV) compared to 60% for HPV (proxy for adolescent vaccination programme) and 52% for seasonal influenza (proxy for adult vaccination programme). Childhood vaccination programmes (e.g., MCV and DTP) had the highest vaccine specific maturity scores, while seasonal influenza and HPV vaccination programmes had much lower scores. The national life course maturity scores ranged from 1 to 23, with a global median of 12 (IQR: 8; 16)., Discussion: The piloted metric provides an overview of the maturity of life course immunization programmes. The metric is structured to be a flexible, rapid resource that can be used to assess other combinations of vaccines across the life course. The findings from this paper provide a baseline of immunization programme maturity for childhood, adolescent, and adult vaccination programmes immediately prior to the COVID-19 vaccine introduction. This maturity score, or adaptations of this approach, could be used to monitor the trajectory of national immunization programme maturity across the life course in the years ahead., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Pneumococcal meningitis, a vaccine-preventable disease caused by Streptococcus pneumoniae (Spn) is the leading bacterial meningitis in under five children. In April 2014, Uganda introduced routine immunization with 10-valent Pneumococcal Conjugate Vaccine (PCV10) for infants. The target coverage for herd immunity is ≥ 90% with three doses (PCV10-dose 3). We assessed the effect of PCV10 introduction and coverage on the trends of pneumococcal meningitis in under five children., Methods: We analyzed laboratory-confirmed pediatric bacterial meningitis (PBM) data at two high-volume WHO-accredited sentinel surveillance hospitals in Kampala City and Gulu District, from 2003 to 2022. We used confirmed cases to estimate the minimum incidence of pneumococcal meningitis in the host districts and calculated annual incidence of pneumococcal meningitis per one million populations, and the proportion of confirmed PBM attributable to Spn. We divided the study period into 2003-2013 (pre-PCV10) and 2014-2022 (post-PCV10), and conducted interrupted time series analysis using autoregressive integrated moving average models for the effect of PCV10 on trends of pneumococcal meningitis and PBM attributable to Spn. We analyzed reported PCV10 data in DHIS2 from 2014 to 2022 for annual PCV10-dose 3 coverage., Results: Among the 534 confirmed PBM cases, 331(62%) were pneumococcal meningitis; 227(69%) from Gulu District and 104(31%) from Kampala City. The majority (95%) of the isolates were not serotyped. The majority (57%) were male and unimmunized (98%); median age = 14(IQR = 6-27) months with most (55%) aged ≥ 12 months. The case-fatality rate was 9%. During Pre-PCV10 period, the overall incidence of pneumococcal meningitis in the host districts increased; slope change = 1.0 (95%CI = 0.99999, 1.00001) but declined in post-PCV10 period (2014-2022) by 92% from 86 cases /1,000,000 in 2014 to 7/1,000,000 in 2022, slope change= -1.00006 (95%CI=-1.00033, -0.99979). Whereas there was an immediate decline in the proportion of confirmed PBM attributable to Spn in the host districts, level change=-1.84611(95%CI=-1.98365,-1.70856), an upward trend was recorded from 2016 to 2022, slope change = 1.0 (95%CI = 0.99997, 1.00003). During 2015-2022, PCV10-dose 3 coverage was largely > 90% for Gulu District and 52-72% for Kampala City., Conclusion: The PCV10 routine immunization program reduced the incidence of pneumococcal meningitis in Kampala City and Gulu District. There was no effect on the confirmed PBM proportionately attributable to Spn. Kampala City persistently recorded PCV10-dose3 coverage < 90%. We recommend enhancing serotyping and periodic nasopharyngeal carriage surveys to ascertain the maximum vaccine effectiveness and monitor Spn serotypes, and strengthening routine immunization in Kampala City., (© 2024. The Author(s).)

Background: Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae), and Neisseria meningitidis (N. meningitidis) are leading causes of childhood bacterial meningitis and preventable by vaccines. The aim of this hospital-based sentinel surveillance is to describe the epidemiological characteristics of pneumococcal meningitis, including disease burden, and to provide baseline data on pneumococcal serotype distribution to support decision making for pneumococcal conjugate vaccine (PCV) introduction in Vietnam., Methods: Surveillance for probable bacterial meningitis in children 1-59 months of age is conducted in three tertiary level pediatric hospitals: one in Hanoi and two in Ho Chi Minh City. Cerebrospinal fluid (CSF) specimens were collected via lumbar puncture from children with suspected meningitis. Specimens were transferred immediately to the laboratory department of the respective hospital for cytology, biochemistry, and microbiology testing, including culture. PCR testing was conducted on CSF specimens for bacterial detection (S. pneumoniae, H. influenzae, and N. meningitidis) and pneumococcal serotyping., Results: During 2015-2018, a total of 1,803 children with probable bacterial meningitis were detected; 1,780 had CSF specimens available for testing. Of 245 laboratory-confirmed positive cases, the majority were caused by S. pneumoniae (229,93.5%). Of those with S. pneumoniae detected, over 70% were caused by serotypes included in currently available PCV products; serotypes 6 A/6B (27.1%), 14 (19.7%), and 23 F (16.2%) were the most common serotypes. Children with laboratory-confirmed pneumococcal meningitis were more likely to live in Hanoi (p < 0.0001) and children 12-23 months of age were at greater odds (OR = 1.65, 95% CI: 1.11, 2.43; p = 0.006) of having confirmed pneumococcal meningitis compared to children < 12 months of age when compared to those without laboratory-confirmed bacterial meningitis. Additionally, children with confirmed pneumococcal meningitis were more likely to exhibit signs and symptoms consistent with clinical meningitis compared to negative laboratory-confirmed meningitis cases (p < 0.0001) and had a greater odds of death (OR = 6.18, 95% CI: 2.98, 12.86; p < 0.0001)., Conclusions: Pneumococcal meningitis contributes to a large burden of bacterial meningitis in Vietnamese children. A large proportion are caused by serotypes covered by PCVs currently available. Introduction of PCV into the routine immunization program could reduce the burden of pneumococcal meningitis in Viet Nam., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

After introducing pneumococcal conjugate vaccines (PCVs), serotype replacement occurred in Streptococcus pneumoniae . Predicting which pneumococcal strains will become common in carriage after vaccination can enhance vaccine design, public health interventions, and understanding of pneumococcal evolution. Invasive pneumococcal isolates were collected during 1998-2018 by the Active Bacterial Core surveillance (ABCs). Carriage data from Massachusetts (MA) and Southwest United States were used to calculate weights. Using pre-vaccine data, serotype-specific inverse-invasiveness weights were defined as the ratio of the proportion of the serotype in carriage to the proportion in invasive data. Genomic data were processed under bioinformatic pipelines to define genetically similar sequence clusters (i.e., strains), and accessory genes (COGs) present in 5-95% of isolates. Weights were applied to adjust observed strain proportions and COG frequencies. The negative frequency-dependent selection (NFDS) model predicted strain proportions by calculating the post-vaccine strain composition in the weighted invasive disease population that would best match pre-vaccine COG frequencies. Inverse-invasiveness weighting increased the correlation of COG frequencies between invasive and carriage data in linear or logit scale for pre-vaccine, post-PCV7, and post-PCV13; and between different epochs in the invasive data. Weighting the invasive data significantly improved the NFDS model's accuracy in predicting strain proportions in the carriage population in the post-PCV13 epoch, with the adjusted R 2 increasing from 0.254 before weighting to 0.545 after weighting. The weighting system adjusted invasive disease data to better represent the pneumococcal carriage population, allowing the NFDS mechanism to predict strain proportions in carriage in the post-PCV13 epoch. Our methods enrich the value of genomic sequences from invasive disease surveillance.IMPORTANCE Streptococcus pneumoniae , a common colonizer in the human nasopharynx, can cause invasive diseases including pneumonia, bacteremia, and meningitis mostly in children under 5 years or older adults. The PCV7 was introduced in 2000 in the United States within the pediatric population to prevent disease and reduce deaths, followed by PCV13 in 2010, PCV15 in 2022, and PCV20 in 2023. After the removal of vaccine serotypes, the prevalence of carriage remained stable as the vacated pediatric ecological niche was filled with certain non-vaccine serotypes. Predicting which pneumococcal clones, and which serotypes, will be most successful in colonization after vaccination can enhance vaccine design and public health interventions, while also improving our understanding of pneumococcal evolution. While carriage data, which are collected from the pneumococcal population that is competing to colonize and transmit, are most directly relevant to evolutionary studies, invasive disease data are often more plentiful. Previously, evolutionary models based on negative frequency-dependent selection (NFDS) on the accessory genome were shown to predict which non-vaccine strains and serotypes were most successful in colonization following the introduction of PCV7. Here, we show that an inverse-invasiveness weighting system applied to invasive disease surveillance data allows the NFDS model to predict strain proportions in the projected carriage population in the post-PCV13/pre-PCV15 and pre-PCV20 epoch. The significance of our research lies in using a sample of invasive disease surveillance data to extend the use of NFDS as an evolutionary mechanism to predict post-PCV13 population dynamics. This has shown that we can correct for biased sampling that arises from differences in virulence and can enrich the value of genomic data from disease surveillance and advance our understanding of how NFDS impacts carriage population dynamics after both PCV7 and PCV13 vaccination., Competing Interests: The authors declare no conflict of interest.

Background: Pneumococcal conjugate vaccines (PCVs) provide strong direct protection in children, while limited data are available on their indirect effect on mortality among older age groups. This multicountry study aimed to assess the population-level impact of pediatric PCVs on all-cause pneumonia mortality among children ≥5 years of age, and invasive pneumococcal disease (IPD) cases in Chile., Methods: Demographic and mortality data from Argentina, Brazil, Chile, Colombia, and Mexico were collected considering the ≥ 5-year-old population, from 2000 to 2019, with 1 795 789 deaths due to all-cause pneumonia. IPD cases in Chile were also evaluated. Time series models were employed to evaluate changes in all-cause pneumonia deaths during the postvaccination period, with other causes of death used as synthetic controls for unrelated temporal trends., Results: No significant change in death rates due to all-cause pneumonia was detected following PCV introduction among most age groups and countries. The proportion of IPD cases caused by vaccine serotypes decreased from 29% (2012) to 6% (2022) among people aged ≥65 years in Chile., Discussion: While an effect of PCV against pneumonia deaths (a broad clinical definition that may not be specific enough to measure indirect effects) was not detected, evidence of indirect PCV impact was observed among vaccine-type-specific IPD cases., Competing Interests: Potential conflicts of interest . D. M. W. has received consulting fees from Pfizer, Merck, Affinivax, and Matrivax for work unrelated to this article; and is Principal Investigator on grants from Pfizer and Merck to Yale University for work unrelated to this article. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in US children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts., Methods: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national health care surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses., Results: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval, 1.8-3.9) visits and 2.4 (95% CI, 1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (95% CI, 11.2-20.4) visits and 13.2 (95% CI, 9.9-18.0) antibiotic prescriptions annually per 1000 children. PCV15/20-additional serotypes account for 0.4% (95% CI, 0.2%-0.6%) and 2.1% (95% CI, 1.5%-3.0%) of pediatric outpatient antibiotic use., Conclusions: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for > 5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use., Competing Interests: Potential conflicts of interest. L. M. K. reports consulting fees from Merck Sharpe & Dohme and Vaxcyte for unrelated work. J. A. L. reports research grants from Pfizer and Merck Sharpe & Dohme; and consulting fees from Pfizer, Merck, Sharpe & Dohme, and Vaxcyte for unrelated work. S. Y. T. reports research grants from Pfizer for unrelated work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Vaccination has been implemented as a priority measure to control infectious diseases worldwide. The aging of the global population continues to intensify, and the process and level of aging in China are more prominent. As age increases, the immune function of people gradually declines, and the consequences of infectious diseases such as influenza, pneumococcal disease, and shingles are more severe in the elderly, which can exacerbate existing underlying diseases, leading to higher medical costs. In the process of achieving healthy aging, it is very necessary to protect vulnerable elderly people through vaccination. Despite the undeniable protective effects of the influenza, pneumococcal, and shingles vaccines for the elderly, coupled with excellent safety and significant health economic benefits, the current vaccination rates for these vaccines among the elderly in China remain low. Some factors, such as insufficient awareness of the necessity of vaccination, concerns about vaccine adverse reactions, lack of systematic and effective recommendations, and imperfect accessibility of vaccination services, affect the popularization of preventive vaccination among the elderly in China. This situation urgently calls for the attention of society as a whole, in order to maximize the role of vaccines in safeguarding the health of the elderly.

Introduction: Understanding the pneumococcal serotypes causing community-acquired pneumonia (CAP) is essential for evaluating the impact of pneumococcal vaccines., Methods: We conducted a prospective surveillance study of adults aged ≥18 years hospitalized with CAP at 3 hospitals in Tennessee and Georgia between 1 September 2018 and 31 October 2022. We assessed for pneumococcal etiology with cultures, the BinaxNOW urinary antigen detection test, and serotype-specific urinary antigen detection assays that detect 30 pneumococcal serotypes contained in the investigational pneumococcal conjugate vaccine V116, as well as licensed vaccines PCV15 and PCV20 (except serotype 15B). The distribution of pneumococcal serotypes was calculated based on serotype-specific urinary antigen detection results., Results: Among 2917 hospitalized adults enrolled with CAP, 352 (12.1%) patients had Streptococcus pneumoniae detected, including 51 (1.7%) patients with invasive pneumococcal pneumonia. The 8 most commonly detected serotypes were: 3, 22F, 19A, 35B, 9N, 19F, 23A, and 11A. Among 2917 adults with CAP, 272 (9.3%) had a serotype detected that is contained in V116, compared to 196 (6.7%) patients with a serotype contained in PCV20 (P < .001), and 168 (5.8%) patients with a serotype contained in PCV15 (P < .001). A serotype contained in V116 but not PCV15 or PCV20 was detected in 120 (4.1%) patients, representing 38.0% of serotype detections., Conclusions: Approximately 12% of adults hospitalized with CAP had S. pneumoniae detected, and approximately one-third of the detected pneumococcal serotypes were not contained in PCV15 or PCV20. Development of new pneumococcal vaccines with expanded serotype coverage has the potential to prevent a substantial burden of disease., Competing Interests: Potential conflicts of interest . This study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. Additionally, the following authors made the following disclosures. K. D. J. reports being an employee and shareholder with stock options of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. C. G. G. reports consulting fees from Merck & Co., Inc and research funding outside the submitted work from NIH, CDC, AHRQ, FDA, and Campbell Alliance/Syneos Health. C. A. R. reports research funding outside the submitted work from BioFire, GSK, MedImmune, Micron, Merck, Novavx, PaxVax, Regeneron, Pfizer, Sanofi-Pasteur, Janssen, Moderna, NIH, and CDC, reports royalties from Meissa Vaccines, and reports 2 planned patents for RSV vaccines. I. Y. reports research funding outside the submitted work from Merck, and consulting fees from Sanofi Pasteur and Merck. T. W. reports being an employee and shareholder with stock options of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. C. R. reports being an employee and shareholder with stock options of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. N. R. reports research funding outside the submitted work from Merck, Sanofi, Pfizer, Vaccine Company, Immorna, Quidel and Lilly, reports consulting fees from Krog, reports honoraria from Virology Education and Medscape, reports support for attending a meeting from Sanofi and Moderna, reports participation in advisory boards for Moderna, Sanofi, Seqirus, Pfizer, EMMES, ICON, and Micron, and reports leadership roles with ARLG, TMRC, CDC-Pertussis challenge, and Clinical Infectious Diseases. The other authors reported no conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Current pneumococcal vaccines, including the pneumococcal polysaccharide (PPV23) and conjugate (PCV13) vaccines, offer protection against specific serotypes but pose risks of serotype replacement that can alter the composition of the nasopharyngeal microbiota. To address this challenge, a novel strategy has been proposed to provide effective protection without disrupting the colonization of other bacterial populations. In our study, we found that subcutaneous immunization with recombinant peptidoglycan N-acetylglucosamine deacetylase A (rPgdA) elicited robust humoral and cellular immune responses, significantly reducing the invasion of Streptococcus pneumoniae in the lungs without affecting nasopharyngeal carriage. Furthermore, rPgdA antisera were shown to diminish bacterial invasion of lung epithelial cells in vitro . Notably, sera from patients with invasive pneumococcal infections exhibited higher levels of antibodies against the PgdA protein compared to sera from healthy adults, suggesting that a natural immune response to this protein occurs during infection. These results suggest a promising new target for the development of pneumococcal vaccines., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Xiao, Liu, Yin and Zhang.)

Background: In early 2021, the 10-valent Pneumococcal conjugate vaccine (PCV10) was replaced with 13-valent (PCV13) by the federal directorate of immunization (FDI), Pakistan. We assessed the impact of a higher valent vaccine, PCV13, on the serotype distribution of nasopharyngeal carriage in rural Pakistan., Methods: Children <2 years were randomly selected from two rural union councils of Matiari, Sindh in Pakistan between September-October,2022. Clinical, sociodemographic and vaccination histories were recorded. Nasopharyngeal swabs were collected and processed at Infectious Disease Research Laboratory, Aga Khan University, Karachi. Whole genome sequencing was performed on the culture positive isolates., Results: Of the 200 children enrolled, pneumococcus was detected in 140(70 %) isolates. Majority of age-eligible children (60.1 %,110/183) received 3 PCV13 doses. PCV10 carriage declined from 13.2 %(78/590) in 2017/18 to 7.2 % (10/140) in 2022, additional PCV13 serotypes (3, 6A/6C and 19A) decreased from 18.5 %(109/590) to 11.4 %(16/140) while non-PCV13 serotypes increased from 68.3 %(403/590) to 81.4 %(114/140). There were 88.5 %(n = 124), 80.7 %(n = 113), 55.0 %(n = 77), and 46.0 %(n = 65) isolates predicted to be resistant to cotrimoxazole, penicillin(meningitis cut-off), tetracycline, and erythromycin respectively., Conclusion: Replacing PCV10 with PCV13 rapidly decreased prevalence of PCV13 carriage among vaccinated children in Matiari, Pakistan. Vaccine-driven selection pressure may have been responsible for the increase of non-PCV13 serotypes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for infants in Argentina's national immunization program (NIP) in a 2 + 1 schedule since 2012. Licensure of the 15-valent vaccine (PCV15) is anticipated soon, and the 20-valent vaccine (PCV20) recently received regulatory approval. This cost-effectiveness analysis examined the public health and economic implications of transitioning from PCV13 to either PCV15 or PCV20 in Argentina's pediatric NIP., Methods: A decision-analytic Markov model was used with a 10-year time horizon and a 3.0% annual discount rate for costs and benefits. Vaccine effectiveness estimates were derived from Argentinian surveillance data, PCV13 clinical effectiveness and impact studies, and PCV7 efficacy studies. Population, epidemiologic, and economic inputs were obtained from literature and Argentinian-specific data. The study adopted a healthcare system perspective; sensitivity and scenario analyses were conducted to assess input parameters and structural uncertainty., Results: Compared with PCV13, PCV20 was estimated to avert an additional 7,378, 42,884, and 172,389 cases of invasive pneumococcal disease (IPD), all-cause pneumonia, and all-cause otitis media (OM), respectively, as well as 3,308 deaths, resulting in savings of United States Dollars (USD) 50,973,962 in direct medical costs. Compared with PCV15, PCV20 was also estimated to have greater benefit, averting an additional 6,140, 35,258, and 142,366 cases of IPD, pneumonia, and OM, respectively, as well as 2,624 deaths, resulting in savings of USD 37,697,868 in direct medical costs. PCV20 was associated with a higher quality-adjusted life year gain and a lower cost (i.e., dominance) versus both PCV13 and PCV15. Results remained robust in sensitivity analyses and scenario assessments., Conclusion: Over a 10-year horizon, vaccination with PCV20 was expected to be the dominant, cost-saving strategy versus PCV13 and PCV15 in children in Argentina. Policymakers should consider the PCV20 vaccination strategy to achieve the greatest clinical and economic benefit compared with lower-valent options., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Lucila Rey-Ares reports a relationship with Pfizer Inc that includes: employment. An Ta reports a relationship with Cytel Inc that includes: employment. An Ta reports a relationship with Pfizer Inc that includes: consulting or advisory. Donata Freigofaite reports a relationship with Cytel Inc that includes: employment. Sophie Warren reports a relationship with Pfizer Inc that includes: employment. Mercedes Mac Mullen reports a relationship with Pfizer Inc that includes: employment. Carolina Carballo reports a relationship with Pfizer Inc that includes: employment. Liping Huang reports a relationship with Pfizer Inc that includes: employment. The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: LRA, CC, and LH are employees of Pfizer Inc. SW and MM were employed by Pfizer Inc. at the time of manuscript development. AT received consulting fees from Pfizer Inc. for the study and manuscript development and is an employee of Cytel Inc. DF was employed by Cytel Inc. at the time of manuscript development. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Since the introduction of vaccines for severe acute respiratory syndrome coronavirus 2 in the United States, there has been significant vaccine hesitancy, in part due to fear of adverse effects. We sought to investigate the rates of smell and taste changes after COVID-19 vaccination compared to other common vaccines. Our study cohort included individuals identified by Current Procedural Terminology code in the TriNetX database receiving the COVID-19 first series, COVID-19 booster, influenza, tetanus, diphtheria, pertussis (TDAP), or pneumococcal vaccines between December 15, 2020, and August 15, 2023. After 1:1 propensity score matching, postvaccination incidence of disturbance of smell and taste was significantly less likely after COVID-19 first series vaccine compared to influenza (odds ratios, OR: 0.27 [95% confidence interval, CI: 0.20-0.36]), TDAP (OR: 0.35 [95% CI: 0.26-0.47]), and pneumococcal vaccines (OR: 0.17 [95% CI: 0.09-0.32]). Similarly, incidence of disturbance of smell and taste was significantly less likely after COVID-19 booster vaccine compared to the influenza (OR: 0.60 [95% CI: 0.48-0.76]), TDAP (OR: 0.63 [95% CI: 0.47-0.85]), and pneumococcal vaccines (OR: 0.44 [95% CI: 0.28-0.68]). This study builds upon the literature demonstrating the safety of COVID-19 vaccination., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Competing Interests: CvM is a principal investigator on a research collaborative grant between Murdoch Children's Research Institute and Pfizer; and has received honoraria from Pfizer for two expert panel meetings and from Merck for a virtual Scientific Input Engagement meeting. PVL declares no competing interests.

Background: The rising incidence of immune-mediated inflammatory diseases (IMID) requires innovative management strategies, including effective vaccination. We aimed to assess the impact of an electronic medical record (EMR)-integrated vaccination tool on vaccination coverage among patients with inflammatory bowel diseases (IBD), rheumatological and dermatological conditions., Methods: A prospective observational study compared vaccination coverage before (2018) and after (2021) implementing the module. Vaccination data for influenza, pneumococcus, hepatitis B and tetanus, and potential predictors were collected from 1430 IMID patients (44.9% male, median age (interquartile range [IQR]) 54 (40-66) years, 789 with IBD, 604 with rheumatological and 37 with dermatological conditions). Data were analysed using McNemar, chi-square tests and multinominal logistic regression., Results: Significant increases in pneumococcus (56.6% to 73.1%, p  < .001) and hepatitis B vaccination (62.2% to 75.9%, p  < .001) were observed. Influenza vaccination rates increased among IBD (76.2% to 80.5%, p  = .006) but remained stable overall (73.1% to 73.2%, p  = 1.000). Tetanus vaccination rates decreased (71.5% to 55.0%, p  < .001). The proportion of fully vaccinated patients (against influenza in the past year for patients >50 years old and/or under immunosuppressive therapy, against pneumococcus in the past 5 years for patients >65 years old and/or under immunosuppressive therapy and additionally against hepatitis B for IBD patients) rose from 41.3% to 54.8% ( p  < .001 all using McNemar). Factors associated with vaccinations included age, immunosuppressive therapy and education level., Conclusions: Increased vaccination coverage was measured after implementing the vaccination tool. The COVID19 pandemic and the 2018 measurement might have increased vaccination awareness. Education of patients and healthcare professionals remains crucial.

Background: The same pneumococcal conjugate vaccines (PCVs) have been used in adults and children in many settings. Differences in the epidemiology of pneumococcal disease between populations necessitates an adult-specific PCV. We aimed to assess the safety, tolerability, and immunogenicity of V116, an investigational 21-valent PCV designed for adults., Methods: This randomised, double-blind, active comparator controlled, international phase 3 trial enrolled adults with or without stable chronic medical conditions at 112 clinical sites in 11 countries or territories. Random assignment was performed using a central electronic interactive response technology system. Cohort 1 (≥50 years) was stratified by age (50-64, 65-74, 75-84, and ≥85 years) and randomised 1:1 to receive one intramuscular dose of V116, or the active comparator, PCV20. Cohort 2 (18-49 years) was randomised 2:1 to receive one intramuscular dose of V116 or PCV20. Pneumococcal serotype-specific opsonophagocytic activity (OPA) and IgG responses were measured before (day 1) and after vaccination (day 30). Four primary immunogenicity outcomes were assessed per-protocol. First, in cohort 1, non-inferiority of V116 to PCV20 was tested using serotype-specific OPA geometric mean titres (GMT) ratios for serotypes common to both vaccines; the lower bound of the 95% CI had to be greater than 0·5 for non-inferiority. Second, superiority of V116 to PCV20 was tested for OPA GMT ratios for the serotypes unique to V116; the lower bound of the 95% CI had to be greater than 2·0 for superiority. Third, superiority of V116 to PCV20 was evaluated by the proportions of participants with a four-fold or greater rise from day 1 to day 30 for serotypes unique to V116; the lower bound of the 95% CI of the differences in proportions (V116 - PCV20) had to be greater than 10% for superiority. Finally, in cohort 2, immunobridging was assessed for all 21 serotypes in V116 for adults aged 18-49 years to 50-64 years; the lower bound of the 95% CI for the OPA GMTs had to be greater than 0·5 for non-inferiority. The safety analysis included all randomly assigned participants who received study vaccine. The primary safety outcome was the proportion of participants with solicited injection site and solicited systemic adverse events until day 5 and vaccine-related serious adverse events up to 6 months after vaccination. This trial is registered at ClinicalTrials.gov (NCT05425732)., Findings: Between July 13, and Nov 22, 2022, 2754 individuals were screened and 2663 participants were randomly assigned. 2656 individuals were vaccinated (1179 in V116 cohort 1; 1177 in PCV20 cohort 1; 200 in V116 cohort 2; and 100 in PCV20 cohort 2). V116 met non-inferiority criteria compared with PCV20 for the ten serotypes common to both vaccines at day 30 in cohort 1 (p<0·0001 for each common serotype). V116 met superiority criteria compared with PCV20 in cohort 1 for ten of the 11 serotypes unique to V116 at day 30 (OPA GMT ratio: p<0·0001 for all unique serotypes except 15C, which was p=0·41; four-fold or greater rise in OPA from day 1-30: p<0·0001 for all serotypes except 15C, which was p=0·67). Immune responses in V116 participants aged 18-49 years were non-inferior compared with V116 participants aged 50-64 years for all V116 serotypes (p<0·0001 for all V116 serotypes). In cohort 1, 685 (58·2%) of participants in V116, and 778 (66·2%) of participants in PCV20 reported one or more adverse event. In cohort 2, 164 (82·0%) participants in V116 and 79 participants (79·0%) in PCV20 reported one or more adverse event. Six deaths were reported, all in cohort 1, none of which were considered vaccine-related (in V116: one due to sepsis, one due to cerebrovascular accident, one due to myocardial infarction, and one due to hepatic cirrhosis and hepatic encephalopathy; in PCV20: one due to cardiac arrest and one due to abdominal abscess). There were no vaccine-related serious adverse events., Interpretation: V116 was non-inferior to PCV20 for the ten serotypes common to both vaccines and superior to PCV20 for all serotypes unique to V116, except for 15C. Immune responses successfully immunobridged between younger and older adults for all serotypes in V116. V116 was generally well tolerated with safety profile similar to PCV20., Funding: Merck Sharp & Dohme, subsidiary of Merck & Co, Rahway, NJ, USA (MSD)., Competing Interests: Declaration of interests CB, LM, DF, WX, MW, JL, UKB, and HLP are employees of Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA (MSD) and may hold stock in Merck & Co, Rahway, NJ, USA. CGG reports serving on an advisory board for MSD and grants or contracts from the National Institutes of Health, the US Centers for Disease Control, Agency for Healthcare and Research Quality, the US Food and Drug Administration, and Syneos Health. JYS reports serving as a principal investigator for this study, and a grant for the investigator-initiated trial from MSD: non-randomized clinical trial to compare the immunogenicity of revaccination with 23-valent pneumococcal polysaccharide vaccine between healthy elderly and those with diabetes in Korea. EB reports clinical trial agreements with MSD, Astra-Zeneca, Janssen, GSK, Clover, and Moderna. DG-H reports serving as a principal investigator for this study. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: The COVID-19 pandemic led to the institution of public health measures in many countries which reduced respiratory infections. We aimed to identify and characterize changes in pediatric (<18 years) invasive pneumococcal disease (pIPD) in Portugal in 2018-2023., Methods: pIPD cases were identified by culture and molecular methods and stratified by age and serotype. When available the susceptibility of the isolates to antimicrobials was evaluated., Results: pIPD cases were markedly reduced in the last trimester of 2019-2020 and the entire 2020-2021 season. While 2021-2022 was in line with pre-pandemic seasons, in 2022-2023, the number of pIPD cases exceeded those found pre-pandemic. Molecular tests were responsible for identifying and serotyping 30% of cases, highlighting their importance in evaluating pIPD. Among the 316 pIPD cases, 37 different serotypes were detected, of which serotypes 3 (n = 85, 26.9%), 8 (n = 25, 7.9%), 10A (n = 21, 6.6%) and 24F (n = 20, 6.3%) were the most frequent. The post-pandemic serotype distribution reflected mostly pre-pandemic trends and the rebound was not driven by particular serotypes. We identified many vaccine failures, most (n = 37) representing serotype 3 infections. Penicillin non-susceptibility increased from 14% pre-pandemic to 29%, with serotype 24F becoming particularly significant., Conclusions: The higher number of cases of pIPD post-COVID-19 in Portugal raises the possibility of a higher burden of pneumococcal disease in Europe post-pandemic. The relatively stable serotype distribution and the current availability of the higher valency conjugate vaccines PCV15 and PCV20, potentially preventing a large proportion of pIPD (43% and 67%, respectively), offer an opportunity to control this increase., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JM-C received research grants administered through his university and received honoraria for serving on the speakers bureaus of Pfizer and Merck Sharp and Dohme. MR received honoraria for serving on the speakers bureau of Pfizer and Merck Sharp and Dohme, for serving in expert panels of Merck Sharp and Dohme, support for attending meetings from Pfizer, and received research grants administered through his university from Merck Sharp and Dohme. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with nephrotic syndrome (NS) are at a higher risk of developing invasive pneumococcal disease (IPD). Pneumococcal carriage studies are helpful tools for detecting potentially infectious serotypes and guiding immunization efforts. Pneumococcal nasopharyngeal colonization is common, and IPD can easily occur in an immunosuppressed state. Limited information is available regarding the frequency of pneumococcal carriage in individuals with NS. The aim of this study was to evaluate pneumococcal carriage and serotype distribution in children with NS., Methods: Pneumococcal carriage was detected by real-time PCR assays from nasopharyngeal swab samples from 98 children with NS, and 100 healthy controls. Isolates were serotyped by real-time PCR., Results: The pneumococcal carriage rate was 44.9% in children with NS. Regarding the recommendation about pneumococcal immunization in children with NS, the vaccination rate was low. Also, non-PCV13 serotypes have been detected in at least 25% of PCV13-vaccinated children. There is no statistically significant difference in total pneumococcal carriage rate, PCV13 serotype carriage rate, or non-PCV13 serotype carriage rate between children with NS and healthy controls (p > 0.05 for all)., Conclusions: The pneumococcal carriage rate was similar between children with NS and healthy controls. However, because children with NS have an increased risk for IPD, the serotype distribution of children with NS can demonstrate the improved protection offered by new pneumococcal vaccines. Regular monitoring for IPD is crucial for assessing the evolving sero-epidemiology of pneumococcal infections and evaluating the effectiveness of vaccines for children with NS., (© 2024. The Author(s).)

Backgroud: Socioeconomic status (SES) plays a vital role in determining vaccination uptake and attitudes. Vaccine hesitancy varies among different communities, yet knowledge of vaccine attitudes among Asian-Americans is limited., Objective: This study aims to investigate the relationship between SES and vaccine attitudes among Asian-Americans in the State of New Jersey (NJ)., Methods: Asian-Americans aged ≥ 18 years living in NJ were included (N = 157). SES was measured by education level, employment type, employment status, and household income. The primary outcomes were vaccine hesitancy, reluctance, and confidence for COVID-19, influenza, and pneumococcal vaccines. Descriptive and inferential statistics were performed. Multivariable logistic regression was used to identify associations between SES and vaccine hesitancy while controlling for confounders such as age, gender, birthplace, and religion., Results: Among 157 participants, 12.1% reported vaccine hesitancy. There was no statistically significant association between vaccine hesitancy and education level (p = 0.68), employment status (p = 1), employment type (p = 0.48), and household income (p = 0.15). Multivariable logistic regression modeling confirmed that none of the SES predictor variables were associated with vaccine hesitancy. However, as exploratory finding, gender was found to be a significant predictor, with males having lower odds of vaccine hesitancy than females (Adjusted OR = 0.14; p < 0.05). Confidence in influenza and pneumococcal vaccines increased during the pandemic, from 62.34% to 70.13% and from 59.2% to 70.51%, respectively. For the COVID-19 vaccine, 73.1% of participants reported having "a lot of confidence" in taking vaccine., Conclusion: Most sampled Asian-Americans in NJ have high confidence in taking COVID-19 vaccines, and there is no significant association between vaccine hesitancy and SES., (© 2024. The Author(s).)

Background: Bacterial etiologies of acute otitis media (AOM) have shifted from the introduction of pneumococcal conjugate vaccines (PCVs), antibiotic selection and competition among species. We characterized Streptococcus pneumoniae ( Spn ), Haemophilus influenzae ( Hflu ) and Moraxella catarrhalis ( Mcat ) in the nasopharynx during well-child healthy visits and at the onset of AOM, and in middle ear fluid (MEF) of children with AOM to assess anticipated effects of higher-valency PCVs (PCV15 and PCV20)., Methods: From September 2021 to September 2023, we conducted a prospective longitudinal cohort study of PCV13 immunized children 6-36 months old. MEF was collected via tympanocentesis. Serotyping and antibiotic susceptibility testing were performed on Spn , Hflu and Mcat isolates., Results: We obtained 825 nasopharyngeal and 216 MEF samples from 301 children. The order of frequency of nasopharyngeal colonization was Mcat , Spn and Hflu ; Hflu was the predominant otopathogen in MEF. Among Spn isolates, non-PCV15, non-PCV20 serotypes predominated in the nasopharynx and in MEF; the most frequent serotype was 35B. Among MEF samples, 30% of Spn isolates were amoxicillin nonsusceptible; 23% of Hflu isolates and 100% of Mcat isolates were β-lactamase-producing., Conclusion: The majority of Spn isolates among young children were non-PCV15, non-PCV20 serotypes, especially serotype 35B; therefore, the impact of higher-valency PCVs in reducing pneumococcal colonization or AOM is expected to be limited. Hflu continues to be the most frequent AOM pathogen. Antibiotic susceptibility data suggest a high dose of amoxicillin/clavulanate or alternative drugs that are effective against contemporary mix of otopathogens could be considered for optimal empiric selection to provide the best efficacy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Single-cell RNA sequencing (scRNA-seq) can resolve transcriptional features from individual cells, but scRNA-seq techniques capable of resolving the variable regions of B cell receptors (BCRs) remain limited, especially from widely-used 3'-barcoded libraries. Here, we report a method that can recover paired, full-length variable region sequences of BCRs from 3'-barcoded scRNA-seq libraries. We first verify this method (B3E-seq) can produce accurate, full-length BCR sequences. We then apply this method to profile B cell responses elicited against the capsular polysaccharide of Streptococcus pneumoniae serotype 3 (ST3) by glycoconjugate vaccines in five infant rhesus macaques. We identify BCR features associated with specificity for the ST3 antigen which are present in multiple vaccinated monkeys, indicating a convergent response to vaccination. These results demonstrate the utility of our method to resolve key features of the B cell repertoire and profile antigen-specific responses elicited by vaccination., (© 2024. The Author(s).)

Background: Adults living with human immunodeficiency virus (ALWHIV) receiving antiretroviral therapy (ART) exhibit higher pneumococcal carriage prevalence than adults without HIV (HIV-). To assess factors influencing high pneumococcal carriage in ALWHIV, we estimated pneumococcal carriage acquisition and clearance rates in a high transmission and disease-burdened setting at least 10 years after introducing infant PCV13 in routine immunisation., Methods: We collected longitudinal nasopharyngeal swabs from individuals aged 18-45 in Blantyre, Malawi. The study group included both HIV- individuals and those living with HIV, categorised based on ART duration as either exceeding 1 year (ART > 1y) or less than 3 months (ART < 3 m). Samples were collected at baseline and then weekly for 16 visits. To detect pneumococcal carriage, we used classical culture microbiology, and to determine pneumococcal serotypes, we used latex agglutination. We modelled trajectories of serotype colonisation using multi-state Markov models to capture pneumococcal carriage dynamics, adjusting for age, sex, number of under 5 year old (< 5y) children, social economic status (SES), and seasonality., Results: We enrolled 195 adults, 65 adults in each of the study groups. 51.8% were females, 25.6% lived with more than one child under 5 years old, and 41.6% lived in low socioeconomic areas. The median age was 33 years (IQR 25-37 years). The baseline pneumococcal carriage prevalence of all serotypes was 31.3%, with non-PCV13 serotypes (NVT) at 26.2% and PCV13 serotypes (VT) at 5.1%. In a multivariate longitudinal analysis, pneumococcal carriage acquisition was higher in females than males (hazard ratio [HR], NVT [1.53]; VT [1.96]). It was also higher in low than high SES (NVT [1.38]; VT [2.06]), in adults living with 2 + than 1 child < 5y (VT [1.78]), and in ALWHIV on ART > 1y than HIV- adults (NVT [1.43]). Moreover, ALWHIV on ART > 1y cleared pneumococci slower than HIV- adults ([0.65]). Residual VT 19F and 3 were highly acquired, although NVT remained dominant., Conclusions: The disproportionately high point prevalence of pneumococcal carriage in ALWHIV on ART > 1y is likely due to impaired nasopharyngeal clearance, which results in prolonged carriage. Our findings provide baseline estimates for comparing pneumococcal carriage dynamics after implementing new PCV strategies in ALWHIV., (© 2024. The Author(s).)

Invasive pneumococcal disease (IPD) due to non-vaccine serotypes after the introduction of pneumococcal conjugate vaccines (PCV) remains a global concern. This study used pathogen genomics to evaluate changes in invasive pneumococcal lineages before, during and after vaccine introduction in South Africa. We included genomes (N = 3104) of IPD isolates from individuals aged <18 years (2005-20), spanning four periods: pre-PCV, PCV7, early-PCV13, and late-PCV13. Significant incidence reductions occurred among vaccine-type lineages in the late-PCV13 period compared to the pre-PCV period. However, some vaccine-type lineages continued to cause invasive disease and showed increasing effective population size trends in the post-PCV era. A significant increase in lineage diversity was observed from the PCV7 period to the early-PCV13 period (Simpson's diversity index: 0.954, 95% confidence interval 0.948-0.961 vs 0.965, 0.962-0.969) supporting intervention-driven population structure perturbation. Increases in the prevalence of penicillin, erythromycin, and multidrug resistance were observed among non-vaccine serotypes in the late-PCV13 period compared to the pre-PCV period. In this work we highlight the importance of continued genomic surveillance to monitor disease-causing lineages post vaccination to support policy-making and future vaccine designs and considerations., (© 2024. The Author(s).)

Background: As part of the Immunisation Agenda 2030, the World Health Organization set a goal to reduce the number of children who did not receive any routine vaccine by 50% by 2030. We aimed to describe the patterns of vaccines received for children with zero, one, and up to full vaccination, while considering newly deployed vaccines (pneumococcal conjugate vaccine (PCV) and rotavirus (ROTA) vaccine) alongside longstanding ones such as the Bacille Calmete-Guérin (BCG), diphtheria, tetanus, and pertussis (DPT), and poliomyelitis vaccines, and measles-containing vaccines (MCVs)., Methods: We used data from national household surveys (Demographic and Health Surveys and Multiple Indicator Cluster Surveys) carried out in 43 low- and middle-income countries since 2014. We calculated the immunisation cascade as a score ranging from zero to six, considering BCG, polio, DPT, and ROTA vaccines, and the MCV and PCV. We also described the most prevalent combination of vaccines. The analyses were pooled across countries and stratified by household wealth quintiles., Results: In the pooled analyses with all countries combined, 9.0% of children failed to receive any vaccines, 58.6% received at least one dose of each of the six vaccines, and 47.2% were fully vaccinated with all doses. Among the few children receiving 1-5 vaccines, the most frequent were BCG vaccines, polio vaccines, DPT vaccines, PCV, ROTA vaccines, and MCV., Conclusions: Targeting children with their initial vaccine is crucial, as those who receive a first vaccine are more likely to undergo subsequent vaccinations. Finding zero-dose children and starting their immunisation is essential to leaving no one behind during the era of Sustainable Development Goals., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: TM and DHR are employed by Gavi, the Vaccine Alliance, the sponsor of this research. The remaining (BCP, TMS, LA, FC, CGV, and AJDB) declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views or policies of the institutions with which they are affiliated., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: In addition to preventing pneumococcal disease, emerging evidence indicates that pneumococcal conjugate vaccines (PCVs) might indirectly reduce viral respiratory tract infections (RTIs) by affecting pneumococcal-viral interactions., Methods: We performed a systematic review of interventional and observational studies published during 2000-2022 on vaccine efficacy/adjusted effectiveness (VE) and overall effect of PCV7, PCV9, PCV10, or PCV13 against viral RTIs., Results: Sixteen of 1671 records identified were included. Thirteen publications described effects of PCVs against viral RTIs in children. VE against influenza ranged between 41% and 86% (n = 4), except for the 2010-2011 influenza season. In a randomized controlled trial, PCV9 displayed efficacy against any viral RTI, human seasonal coronavirus, parainfluenza, and human metapneumovirus. Data in adults were limited (n = 3). PCV13 VE was 4%-25% against viral lower RTI, 32%-35% against coronavirus disease 2019 outcomes, 24%-51% against human seasonal coronavirus, and 13%-36% against influenza A lower RTI, with some 95% confidence intervals spanning zero. No protection was found against adenovirus or rhinovirus in children or adults., Conclusions: PCVs were associated with protection against some viral RTI, with the strongest evidence for influenza in children. Limited evidence for adults was generally consistent with pediatric data. Restricting public health evaluations to confirmed pneumococcal outcomes may underestimate the full impact of PCVs., Competing Interests: Potential conflicts of interest. G. H., I. T. S., S. M., and M. B. are employees of P95 Epidemiology and Pharmacovigilance, which received funding from Pfizer to conduct the research described in this manuscript and for manuscript development. G. H. has also received personal fees from MSD, Sanofi Pasteur, Janssen, SNB, and Pfizer as speaker at an international meeting and as a member of advisory boards, outside the scope of the submitted work. E. M. D., L. J., C. T., and B. D. G. are employees of Pfizer, Inc, and may hold stocks or stock options. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Sickle cell anemia (SCA) is a hereditary blood disorder characterized by the production of abnormal hemoglobin, leading to the formation of sickle-shaped red blood cells. These distorted cells can obstruct blood flow, causing vaso-occlusive crises and increasing the risk of severe infections due to functional asplenia and immune system dysregulation. Immunization is a crucial strategy to mitigate infection-related complications in individuals with SCA, necessitating a comprehensive and tailored vaccination approach. Current immunization guidelines for individuals with SCA recommend a combination of standard and additional vaccines to address their heightened susceptibility to infections. Key vaccines include pneumococcal conjugate (PCV13) and polysaccharide (PPSV23) vaccines, meningococcal conjugate (MenACWY) and serogroup B (MenB) vaccines, Haemophilus influenzae type b (Hib) vaccine, annual influenza vaccine, and hepatitis A and B vaccines. These vaccinations aim to provide broad protection against pathogens that pose significant risks to patients with SCA. Despite generally adequate immune responses, the variability in vaccine efficacy due to immune dysfunction necessitates booster doses and additional vaccinations. This narrative review highlights the importance of adhering to current immunization recommendations and addresses challenges such as access to care, vaccine hesitancy, and monitoring vaccination status., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Diseases caused by S. pneumoniae are the leading cause of child mortality. As antibiotic resistance of S. pneumoniae is rising, vaccination remains the most recommended solution. However, the existing pneumococcal polysaccharides vaccine (Pneumovax ® 23) proved only to induce T-independent immunity, and strict cold chain dependence of the protein conjugate vaccine impedes its promotion in developing countries, where infections are most problematic. Affordable and efficient vaccines against pneumococcus are therefore in high demand. Here, we present an intranasal vaccine Lipo + CPS12F&αGC, containing the capsular polysaccharides of S. pneumoniae 12F and the iNKT agonist α-galactosylceramide in cationic liposomes. In BALB/cJRj mice, the vaccine effectively activates iNKT cells and promotes B cells maturation, stimulates affinity-matured IgA and IgG production in both the respiratory tract and systemic blood, and displays sufficient protection both in vivo and in vitro. The designed vaccine is a promising, cost-effective solution against pneumococcus, which can be expanded to cover more serotypes and pathogens., (© 2024. The Author(s).)

Streptococcus pneumoniae carriage studies are crucial to monitor changes induced by use of pneumococcal conjugate vaccines and inform vaccination policies. In this cross-sectional study, we examined changes within the pneumococcal population following introduction of PCV13 in 2015 in the National Immunization Program (NIP), in Portugal. In 2018-2020 (NIP-PCV13), we obtained 1450 nasopharyngeal samples from children ≤6 years attending day-care. We assessed serotypes, antimicrobial resistance, and genotypes (MLST and GPSC) and compared findings with earlier periods: 2009-2010 (pre-PCV13), 2011-2012 (early-PCV13), and 2015-2016 (late-PCV13). Pneumococcal carriage prevalence remained stable at 60.2 %. Carriage of PCV13 serotypes was 10.7 %, markedly reduced compared to pre-PCV13 period (47.6 %). The most prevalent PCV13 serotypes were 19F, 3, and 19A all showing a significant decreasing trend compared to the pre-PCV13 period (from 7.1 % to 4.7 %, 10.1 % to 1.8 %, and 14.1 % to 1.8 %, respectively), a notable observation given the described limited effectiveness of PCV13 against serotype 3. Non-vaccinated children and children aged 4-6 years were more likely to carry PCV13 serotypes (2.5-fold, 95 %CI [1.1-5.6], and 2.9-fold, 95 %CI [1.3-6.8], respectively). The most prevalent non-PCV13 serotypes were 15B/C, 11A, 23B, 23A, and NT, collectively accounting for 51.9 % of all isolates. In total, 30.5 % of all pneumococci were potentially covered by PCV20. Resistance to penicillin (low-level) and macrolides increased significantly, from 9.3 % and 13.4 %, respectively, in the late-PCV13 period, to approximately 20 % each, mostly due to lineages expressing non-PCV13 serotypes, nearing pre-PCV13 levels. An expansion of lineages traditionally associated with PCV13 serotypes, like CC156-GPSC6 (serotype 14) and CC193-GPSC11 (serotype 19F), but now predominantly expressing non-PCV13 serotypes (11A, 15B/C, and 24F for GPSC6; and 15A and 21 for GPSC11) was noted. These findings indicate that the pneumococcal population is adapting to the pressures conferred by PCV13 and antimicrobial use and indicate the need to maintain close surveillance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RSL has received consulting and speaking fees from Pfizer and Merck Sharp & Dome. RSL has received funds for unrestricted research grants from Pfizer and Merck Sharp & Dome, paid directly to her institution. ABA has received consulting and speaking fees from Pfizer and Merck Sharp & Dome. All other authors declare they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pneumococcal disease in older adults in the United Kingdom is rising despite immunisation. A key gap in the literature is the clinical effectiveness of revaccination with the pneumococcal polysaccharide vaccine (PPV23)., Methods: A cohort study was performed in England, using electronic medical records in the Clinical Practice Research Datalink. Individuals aged ≥64 years and vaccinated with PPV23 were included. Rates of hospitalised pneumonia (HP) and invasive pneumococcal disease (IPD) were compared between individuals receiving a single PPV23 dose versus those receiving two doses using multi-level Cox proportional hazards models. Propensity score weighting was performed to minimise the effect of confounding covariates across the comparison groups., Results: Between 2006 and 2019, there were 462 505 eligible participants. Of those, 6747 (1·5 %) received revaccination. Two doses compared to one dose was associated with an increased risk of HP (adjusted Hazard Ratio [aHR] 1·95; 95 %CI 1·74-2·20) and IPD (aHR 1·44; 95 %CI 1·41-1·46). In participants aged 64-74 years PPV23 revaccination was associated with more IPD (aHR 2·02; 95 %CI 1·75-2·33) and HP (aHR 1·46; 95 %CI 1·42-1.49). In those aged ≥75 years PPV23 revaccination was associated with more HP (aHR 1·12; 95 %CI 1·08-1·16) with no statistically significant difference detected in risk of IPD (aHR 1·20; 95 %CI 0·94-1·52)., Conclusions: No clear benefit of PPV23 revaccination was measured in older adults in this observational study. The small proportion of revaccinated subjects limits the strength of the conclusions. Further research evaluating the clinical effectiveness of PPV23 revaccination is required., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NF and DH are currently in receipt of grant support from Seqirus UK Ltd. for the evaluation of influenza vaccines in the UK. NF and DH have previously received research-initiated and industry-initiated research grant support from GlaxoSmithKline (GSK) Biologicals for evaluation of rotavirus vaccination in the UK. DH has also received grants from GSK, Sanofi Pasteur, and Merck & Co (Kenilworth, New Jersey, USA) for rotavirus strain surveillance. KD, VD, LB, SA, NB and KF have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Immunogenicity of influenza and pneumococcal vaccines varies and requires further elucidation in patients with multiple sclerosis (MS) under treatment with disease-modifying therapies (DMTs)., Methods: Adult MS patients who consented with vaccination after standard-of-care consultation by their treating physicians were enrolled. All received a single dose of an inactivated quadrivalent influenza vaccine and of the 23-valent pneumococcal vaccine. A blood sample was collected before and after four weeks of vaccination for measurement of antibodies against Influenza A, B and S. pneumoniae. Patients were followed-up for adverse events and MS relapse for 12 months., Results: One hundred and seventy-two patients (65.7 % female, mean age 42 ± 13 years old, mean MS duration 7.6 ± 7.2 years, 81.4 % under DMTs) were enrolled from November 2019 to March 2020. Antibody measurements were available for 151 patients. Seropositivity for anti-PPSV23 did not differ between baseline and at 4 weeks of follow-up (n = 56, 37.1 %). There was a significant increase of absolute antibody titers post-vaccination for both influenza A and B (p < 0.001). For Influenza A, seropositivity was evident for 57 (37.7 %) patients at 4 weeks compared to 19 (12.6 %) patients at baseline (p McNemar  < 0.001). For Influenza Β, 110 (72.8 %) seroconverted 4 weeks after vaccination compared to 12 (7.9 %) at baseline (p McNemar  < 0.001). Interferon and fumarate did not affect influenza seroconversion while rituximab was associated with lower titers. Mild local AEs (pain, edema) were observed in 23.8 %; no severe AE was reported. Thirty-four patients (19.8 %) had a relapse during the 12-month follow-up; none was attributed to the vaccination., Conclusions: Seroconversion in MS patients on treatment was more frequent following influenza compared to PPSV23 vaccination. Rituximab had an effect on the height of the immune response. Better immunization coverage as well as future evaluation of the breadth of immune response elicited by immunization is necessary for these patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)