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Neisseria gonorrhoeae is widespread globally. Primary prevention is unsuccessful and antimicrobial resistance threatens optimal management. There is no specific vaccine and natural infection studies show that N gonorrhoeae can avoid and suppress immune responses. In addition to extensive variation in expression and specificity of many gonococcal surface antigens, it induces a robust inflammatory response through the Th17 pathway with a large influx of neutrophils and inflammatory cytokines but evades macrophages. The Th1- and Th2-mediated response is suppressed, resulting in low, short-lived antibody titers. Real-world evidence suggests that gonorrhea cases are reduced among recipients of Neisseria meningitidis group B vaccines containing outer membrane vesicles (OMVs). Although the first randomized trial of an OMV-containing MenB vaccine against N gonorrhoeae infection did not show statistically significant vaccine efficacy, ongoing trials might shed further light. Several candidate vaccine antigens for a gonococcal-specific vaccine are being evaluated preclinically but only one has reached clinical trials. [ABSTRACT FROM AUTHOR]

Background Rotavirus is a leading cause of severe pediatric gastroenteritis; 2 highly effective vaccines are used in the United States (US). We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort. Methods Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal (PREVAIL) is a birth cohort of 245 mother-child pairs enrolled in 2017–2018 and followed for 2 years. Infant stool samples and symptom information were collected weekly. Shedding was defined as reverse-transcription polymerase chain reaction detection of rotavirus vaccine virus in stools collected 4–28 days after dose 1. Seroconversion was defined as a 3-fold rise in immunoglobulin A between the 6-week and 6-month blood draws. Correlates were analyzed using generalized estimating equations and logistic regression. Results Prevaccination immunoglobulin G (IgG) (odds ratio [OR], 0.84 [95% confidence interval {CI},.75–.94] per 100-unit increase) was negatively associated with shedding. Shedding was also less likely among infants with a single-nucleotide polymorphism inactivating FUT2 antigen secretion ("nonsecretors") with nonsecretor mothers, versus all other combinations (OR, 0.37 [95% CI,.16–.83]). Of 141 infants with data, 105 (74%) seroconverted; 78 (77%) had shed vaccine virus following dose 1. Prevaccination IgG and secretor status were significantly associated with seroconversion. Neither shedding nor seroconversion significantly differed by vaccine product. Conclusions In this US cohort, prevaccination IgG and maternal and infant secretor status were associated with rotavirus vaccine response. [ABSTRACT FROM AUTHOR]

Background With coronavirus disease 2019 (COVID-19) vaccination no longer mandated by many businesses/organizations, it is now up to individuals to decide whether to get any new boosters/updated vaccines going forward. Methods We developed a Markov model representing the potential clinical/economic outcomes from an individual perspective in the United States of getting versus not getting an annual COVID-19 vaccine. Results For an 18–49 year old, getting vaccinated at its current price ($60) can save the individual on average $ 30–$603 if the individual is uninsured and $4–$437 if the individual has private insurance, as long as the starting vaccine efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is ≥50% and the weekly risk of getting infected is ≥0.2%, corresponding to an individual interacting with 9 other people in a day under Winter 2023–2024 Omicron SARS-CoV-2 variant conditions with an average infection prevalence of 10%. For a 50–64 year old, these cost-savings increase to $111–$1278 and $119–$1706 for someone without and with insurance, respectively. The risk threshold increases to ≥0.4% (interacting with 19 people/day), when the individual has 13.4% preexisting protection against infection (eg, vaccinated 9 months earlier). Conclusions There is both clinical and economic incentive for the individual to continue to get vaccinated against COVID-19 each year. [ABSTRACT FROM AUTHOR]

Background The RTS,S/AS01E (RTS,S) malaria vaccine is recommended for children in malaria endemic areas. This phase 2b trial evaluates RTS,S fractional- and full-dose regimens in Ghana and Kenya. Methods In total, 1500 children aged 5–17 months were randomized (1:1:1:1:1) to receive RTS,S or rabies control vaccine. RTS,S groups received 2 full RTS,S doses at months 0 and 1 and either full (groups R012-20, R012-14-26) or fractional doses (one-fifth; groups Fx012-14-26, Fx017-20-32). Results At month 32 post-dose 1, vaccine efficacy against clinical malaria (all episodes) ranged from 38% (R012-20; 95% confidence interval [CI]: 24%–49%) to 53% (R012-14-26; 95% CI: 42%–62%). Vaccine impact (cumulative number of cases averted/1000 children vaccinated) was 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), and 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional vs full dose; post hoc analysis), we estimated cases averted/1000 RTS,S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), and 880 (Fx017-20-32). Conclusions Vaccine efficacy was similar across RTS,S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If maintained through trial end, these observations underscore the means to reduce cost per regimen thus maximizing impact and optimizing supply. Clinical Trials Registration NCT03276962 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Background The aim of the current study was to determine the safety and immunogenicity of trivalent inactivated influenza vaccine (TIV) alone or formulated with Advax delta inulin adjuvant in those who were older (aged >60 years) or had chronic disease. Methods Over 4 consecutive years from 2008 through 2011, adult participants with chronic disease or >60 years of age were recruited into a randomized controlled study to assess the safety, tolerability and immunogenicity of Advax-adjuvanted TIV (TIV + Adj) versus standard TIV. The per-protocol population with ≥1 postbaseline measurement of influenza antibodies comprised 1297 participants, 447 in the TIV and 850 in the TIV + Adj) group. Results No safety issues were identified. Variables negatively affecting vaccine responses included obesity and diabetes mellitus. Advax adjuvant had a positive impact on anti-influenza immunoglobulin M responses and on H3N2 and B strain seropositivity as assessed by hemagglutination inhibition. Conclusions TIV + Adj was safe and well tolerated in individuals with chronic disease. There is an ongoing need for research into improved influenza vaccines for high-risk populations. Clinical Trials Registration Australia New Zealand Clinical Trial Registry: ACTRN 12608000364370. [ABSTRACT FROM AUTHOR]

Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. Severe acute respiratory syndrome coronavirus 2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic messenger RNA vaccine response in retrospective and prospective cohorts with lymphoma and chronic lymphocytic leukemia, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active treatment, but nonresponse was also common within observation and posttreatment groups. Total immunoglobulin A and immunoglobulin M correlated with successful vaccine response. In individuals treated with anti-CD19–directed chimeric antigen receptor–modified T cells, nonresponse was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to individualize vaccine timing. [ABSTRACT FROM AUTHOR]

Background The hemagglutination inhibition antibody (HAI) titer contributes only a part of vaccine-induced protection against influenza virus infections. Using causal mediation analysis, we quantified the proportion of vaccine efficacy mediated by postvaccination HAI titers. Methods We conducted causal mediation analyses using data from a randomized, active-comparator controlled, phase III, trial of an inactivated, split-virion seasonal quadrivalent influenza vaccine in children conducted from October 2010 to December 2011 in 8 countries. Vaccine efficacy was estimated using a weighted Cox proportional hazards model. Estimates were decomposed into the direct and indirect effects mediated by postvaccination HAI titers. Results The proportions of vaccine efficacy mediated by postvaccination HAI titers were estimated to be 22% (95% confidence interval, 18%-–47%) for influenza A(H1N1), 20% (16%–39%) for influenza A(H3N2), and 37% (26%–85%) for influenza B/Victoria. Conclusions HAI titers partially mediate influenza vaccine efficacy against influenza A(H1N1), A(H3N2), and B/Victoria. Our estimates were lower than in previous studies, possibly reflecting expected heterogeneity in antigenic similarity between vaccine and circulating viruses across seasons. [ABSTRACT FROM AUTHOR]

Background We assessed associations between binding antibody (bAb) concentration <5 days from symptom onset and testing positive for COVID-19 among patients in a test-negative study. Methods From October 2021 to June 2022, study sites in 7 states enrolled patients aged ≥6 months presenting with acute respiratory illness. Respiratory specimens were tested for SARS-CoV-2. In blood specimens, we measured concentrations of anti-SARS-CoV-2 antibodies against the spike protein receptor binding domain (RBD) and nucleocapsid antigens from the ancestral strain in standardized bAb units (BAU). Percentage change in odds of COVID-19 by increasing anti-RBD bAb was estimated via logistic regression as (1 – adjusted odds ratio of COVID-19) × 100, adjusting for COVID-19 mRNA vaccine doses, age, site, and high-risk exposure. Results Out of 2018 symptomatic patients, 662 (33%) tested positive for acute SARS-CoV-2 infection. Geometric mean RBD bAb levels were lower among COVID-19 cases than SARS-CoV-2 test-negative controls during the Delta-predominant period (112 vs 498 BAU/mL) and Omicron-predominant period (823 vs 1189 BAU/mL). Acute-phase ancestral spike RBD bAb levels associated with 50% lower odds of COVID-19 were 1968 BAU/mL against Delta and 3375 BAU/mL against Omicron; thresholds may differ in other laboratories. Conclusions During acute illness, antibody concentrations against ancestral spike RBD were associated with protection against COVID-19. [ABSTRACT FROM AUTHOR]

Background The 2022–2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed. Methods Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022–2023 season against influenza A–associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022 to March 2023 among adults (aged ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test positive by molecular assay) and controls (influenza test negative), applying inverse-propensity-to-be-vaccinated weights. Results The analysis included 85 389 ED/UC ARI encounters (17.0% influenza A positive; 37.8% vaccinated overall) and 19 751 hospitalizations (9.5% influenza A positive; 52.8% vaccinated overall). VE against influenza A–associated ED/UC encounters was 44% (95% confidence interval [CI], 40%–47%) overall and 45% and 41% among adults aged 18–64 and ≥65 years, respectively. VE against influenza A–associated hospitalizations was 35% (95% CI, 27%–43%) overall and 23% and 41% among adults aged 18–64 and ≥65 years, respectively. Conclusions VE was moderate during the 2022–2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources. [ABSTRACT FROM AUTHOR]

Background Randomized trials conducted in low- and middle-income settings demonstrated efficacy of influenza vaccination during pregnancy against influenza infection among infants <6 months of age. However, vaccine effectiveness (VE) estimates from settings with different population characteristics and influenza seasonality remain limited. Methods We conducted a test-negative study in Ontario, Canada. All influenza virus tests among infants <6 months from 2010 to 2019 were identified and linked with health databases to ascertain information on maternal-infant dyads. VE was estimated from the odds ratio for influenza vaccination during pregnancy among cases versus controls, computed using logistic regression with adjustment for potential confounders. Results Among 23 806 infants tested for influenza, 1783 (7.5%) were positive and 1708 (7.2%) were born to mothers vaccinated against influenza during pregnancy. VE against laboratory-confirmed infant influenza infection was 64% (95% confidence interval [CI], 50%–74%). VE was similar by trimester of vaccination (first/second, 66% [95% CI, 40%–80%]; third, 63% [95% CI, 46%–74%]), infant age at testing (0 to <2 months, 63% [95% CI, 46%–75%]; 2 to <6 months, 64% [95% CI, 36%–79%]), and gestational age at birth (≥37 weeks, 64% [95% CI, 50%–75%]; < 37 weeks, 61% [95% CI, 4%–86%]). VE against influenza hospitalization was 67% (95% CI, 50%–78%). Conclusions Influenza vaccination during pregnancy offers effective protection to infants <6 months, for whom vaccines are not currently available. [ABSTRACT FROM AUTHOR]

Background Antigenic similarity between vaccine viruses and circulating viruses is crucial for achieving high vaccine effectiveness against seasonal influenza. New non-egg-based vaccine production technologies could revise current vaccine formulation schedules. We aim to assess the potential benefit of delaying seasonal influenza vaccine virus selection decisions. Methods We identified seasons where season-dominant viruses presented increasing prevalence after vaccine formulation had been decided in February for the Northern Hemisphere, contributing to their antigenic discrepancy with vaccine viruses. Using a SEIR (susceptible-exposed-infectious-recovered) model of seasonal influenza in the United States, we evaluated the impact of updating vaccine decisions with more antigenically similar vaccine viruses on the influenza burden in the United States. Results In 2014–2015 and 2019–2020, the season-dominant A(H3N2) subclade and B/Victoria clade, respectively, presented increasing prevalence after vaccine decisions were already made for the Northern Hemisphere. Our model showed that the updated A(H3N2) vaccine could have averted 5000–65 000 influenza hospitalizations in the United States in 2014–2015, whereas updating the B/Victoria vaccine component did not substantially change influenza burden in the 2019–2020 season. Conclusions With rapid vaccine production, revising current timelines for vaccine selection could result in substantial epidemiological benefits, particularly when additional data could help improve the antigenic match between vaccine and circulating viruses. [ABSTRACT FROM AUTHOR]

Background Even moderate differences in rotavirus vaccine effectiveness against nonvaccine genotypes may exert selective pressures on circulating rotaviruses. Whether this vaccine effect or natural temporal fluctuations underlie observed changes in genotype distributions is unclear. Methods We systematically reviewed studies reporting rotavirus genotypes from children <5 years of age globally between 2005 and 2023. We compared rotavirus genotypes between vaccine-introducing and nonintroducing settings globally and by World Health Organization (WHO) region, calendar time, and time since vaccine introduction. Results Crude pooling of genotype data from 361 studies indicated higher G2P[4], a nonvaccine genotype, prevalence in vaccine-introducing settings, both globally and by WHO region. This difference did not emerge when examining genotypes over time in the Americas, the only region with robust longitudinal data. Relative to nonintroducing settings, G2P[4] detections were more likely in settings with recent introduction (eg, 1–2 years postintroduction adjusted odds ratio [aOR], 4.39; 95% confidence interval [CI], 2.87–6.72) but were similarly likely in settings with more time elapsed since introduction, (eg, 7 or more years aOR, 1.62; 95% CI,.49–5.37). Conclusions When accounting for both regional and temporal trends, there was no substantial evidence of long-term vaccine-related selective pressures on circulating genotypes. Increased prevalence of G2P[4] may be transient after rotavirus vaccine introduction. [ABSTRACT FROM AUTHOR]

Developing new adjuvants that can effectively induce humoral and cellular immune responses while broadening the immune response is of great value. In this study, we aimed to develop single-stranded RNA adjuvants expressing (1) granulocyte monocyte colony-stimulating factor or (2) interleukin 18 based on the encephalomyocarditis virus internal ribosome entry site; we also tested their efficacy in combination with ovalbumin or inactivated influenza vaccines. Notably, cytokine-expressing RNA adjuvants increased the expression of antigen-presenting cell activation markers in mice. Specifically, when combined with ovalbumin, RNA adjuvants expressing granulocyte monocyte colony-stimulating factor increased CD4+ T-cell responses, while those expressing interleukin 18 increased CD8+ T-cell responses. Cytokine-expressing RNA adjuvants further increased the frequency of polyclonal T cells with the influenza vaccine and reduced the clinical illness scores and weight loss of mice after viral challenge. Collectively, our results suggest that cytokine-expressing RNA adjuvants can be applied to protein-based or inactivated vaccines to increase their efficacy. [ABSTRACT FROM AUTHOR]

Background Cell-based quadrivalent-inactivated influenza vaccine has been shown to have higher vaccine effectiveness than traditional egg-based quadrivalent-inactivated influenza vaccine. This is observed despite similar levels of serum hemagglutinin antibodies induced by each vaccine. Methods In this study, we examine peripheral immune activation after egg-based or cell-based influenza vaccination in a clinical trial in children. Peripheral blood mononuclear cells were isolated, and ribonucleic acid was sequenced from 81 study participants (41 Fluzone, egg based and 40 Flucelvax, cell based) pre- and 7 days postvaccination. Seroconversion was assessed by hemagglutinin inhibition assay. Differential gene expression was determined and pathway analysis was conducted. Results Cell-based influenza vaccine induced greater interferon-stimulated and innate immune gene activation compared with egg-based influenza vaccine. Participants who seroconverted had increased interferon-signaling activation versus those who did not seroconvert. Conclusions These data suggest that cell-based influenza vaccine stimulates immune activation differently from egg-based influenza vaccine, shedding light on reported differences in vaccine effectiveness. [ABSTRACT FROM AUTHOR]

Background Histo-blood group antigen (HBGA) status may affect vaccine efficacy due to rotavirus strains binding to HBGAs in a P genotype–dependent manner. This study aimed to determine if HBGA status affected vaccine take of the G3P[6] neonatal vaccine RV3-BB. Methods DNA was extracted from stool samples collected in a subset (n = 164) of the RV3-BB phase IIb trial in Indonesian infants. FUT2 and FUT3 genes were amplified and sequenced, with any single-nucleotide polymorphisms analyzed to infer Lewis and secretor status. Measures of positive cumulative vaccine take were defined as serum immune response (immunoglobulin A or serum-neutralizing antibody) and/or stool excretion of RV3-BB virus. Participants were stratified by HBGA status and measures of vaccine take. Results In 147 of 164 participants, Lewis and secretor phenotype were determined. Positive vaccine take was recorded for 144 (97.9%) of 147 participants with the combined phenotype determined. Cumulative vaccine take was not significantly associated with secretor status (relative risk, 1.00 [95% CI,.94–1.06]; P =.97) or Lewis phenotype (relative risk, 1.03 [95% CI,.94–1.14]; P =.33), nor was a difference observed when analyzed by each component of vaccine take. Conclusions The RV3-BB vaccine produced positive cumulative vaccine take, irrespective of HBGA status in Indonesian infants. [ABSTRACT FROM AUTHOR]

Background Solid organ transplant recipients (SOTRs) are at higher risk for severe infection. However, the risk for severe COVID-19 and vaccine effectiveness among SOTRs remain unclear. Methods This retrospective study used a nationwide health care claims database and COVID-19 registry from the Republic of Korea (2020 to 2022). Adult SOTRs diagnosed with COVID-19 were matched with up to 4 non-SOTR COVID-19 patients by propensity score. Severe COVID-19 was defined as treatment with high-flow nasal cannulae, mechanical ventilation, or extracorporeal membrane oxygenation. Results Among 6783 SOTRs with COVID-19, severe COVID-19 was reported with the highest rate in lung transplant recipients (13.16%), followed by the heart (6.30%), kidney (3.90%), and liver (2.40%). SOTRs had a higher risk of severe COVID-19 compared to non-SOTRs, and lung transplant recipients showed the highest risk (adjusted odds ratio, 18.14; 95% confidence interval [CI], 8.53–38.58). Vaccine effectiveness against severe disease among SOTRs was 47% (95% CI, 18%–65%), 64% (95% CI, 49%–75%), and 64% (95% CI, 29%–81%) for 2, 3, and 4 doses, respectively. Conclusions SOTRs are at significantly higher risk for severe COVID-19 compared to non-SOTRs. Vaccination is effective in preventing the progression to severe COVID-19. Efforts should be made to improve vaccine uptake among SOTRs, while additional protective measures should be developed. [ABSTRACT FROM AUTHOR]

Several immunization products are currently being developed against respiratory syncytial virus (RSV) for children, pregnant females, and older adults, and some products have already received authorization. Therefore, studies to monitor the effectiveness of these products are needed in the following years. To assist researchers to conduct postmarketing studies, we developed a generic protocol for register-based cohort studies to evaluate immunization product effectiveness against RSV-specific and nonspecific outcomes. To conduct a study on the basis of this generic protocol, the researchers can use any relevant databases or healthcare registers that are available at the study site. [ABSTRACT FROM AUTHOR]

We estimated the effectiveness of booster doses of monovalent and bivalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults aged ≥50 years in Ontario, Canada. Monovalent and bivalent mRNA COVID-19 booster doses provided similar strong initial protection against severe outcomes. Uncertainty remains around waning of protection from these vaccines. [ABSTRACT FROM AUTHOR]

Background The United States has experienced a resurgence of pertussis following the introduction of acellular pertussis (aP) vaccines. This is likely due to the failure of aP vaccines to induce durable immunity and prevent infection, carriage, and transmission. Methods To evaluate the impact of aP vaccination on the immune response to infection and test the ability of infection to reprogram aP-imprinted immune responses, we challenged unvaccinated and aP-vaccinated baboons with Bordetella pertussis multiple times and accessed the immune responses and outcomes of infections after each exposure. Results Multiple infections were required to elicit T-helper 17 responses and protection in aP-vaccinated animals comparable to responses seen in unvaccinated animals after a single challenge. Even after 3 challenges, T-helper 1 responses were not observed in aP-vaccinated animals. Immunoglobulin G responses to vaccine and nonvaccine antigens were not negatively affected in aP-vaccinated animals. Conclusions Our results indicate that it is possible to retrain aP-primed immune responses, but it will likely require an optimal booster and multiple doses. Our results in the baboon model suggest that circulation of B. pertussis in aP-vaccinated populations is concentrated in the younger age bands of the population, providing information that can guide improved modeling of B. pertussis epidemiology in aP-vaccinated populations. [ABSTRACT FROM AUTHOR]

Background This phase 2 extension explored the long-term antibody persistence of an investigational Clostridioides difficile vaccine and the safety, tolerability, and immunogenicity of dose 4 approximately 12 months post–dose 3. Methods One year post–dose 3, healthy US 65- to 85-year-olds (N = 300) were randomized to dose 4 of vaccine at previously received antigen levels (100 or 200 μg) or placebo. Assessments included safety and percentages of participants achieving neutralizing antibody titers above prespecified thresholds (≥219 and ≥2586 neutralization units/mL for toxins A and B, respectively). Results In participants previously given three 200-µg doses and placebo in the extension, toxin A and B neutralizing antibodies were above prevaccination levels 48 months post–dose 3 (36 months after placebo); 24.0% and 26.0% had toxin A and B antibodies at or above prespecified thresholds, respectively. Neutralizing antibodies increased post–dose 4 (12 months post–dose 3) and persisted to 36 months post–dose 4. Thirty days post–dose 4, all participants had toxin A and 86.5% to 100% had toxin B titers at or above prespecified thresholds. Local reactions were more frequent in vaccine recipients. Systemic and adverse event frequencies were similar across groups. Conclusions C difficile vaccine immune responses persisted 48 months post–dose 3. Dose 4 was immunogenic and well tolerated, supporting continued development. Clinical Trials Registration. ClinicalTrials.gov NCT02561195. [ABSTRACT FROM AUTHOR]

Using a prospective, observational cohort study during the post–"dynamic COVID-zero" wave in China, we estimated short-term relative effectiveness against Omicron BA.5 infection of inhaled aerosolized adenovirus type 5–vectored ancestral strain coronavirus disease 2019 (COVID-19) vaccine as a second booster dose approximately 1 year after homologous boosted primary series of inactivated COVID-19 vaccine compared with no second booster. Participants reported nucleic acid or antigen test results weekly until they tested positive or completed predesignated follow-up. After excluding participants infected <14 days after study entry, relative effectiveness among the 6576 participants was 61% in 18- to 59-year-olds and 38% in ≥60-year-olds and was sustained for 12 weeks. [ABSTRACT FROM AUTHOR]

Background Protection against herpes zoster is primarily conferred by cell-mediated immunity. However, anti–varicella-zoster virus (VZV) glycoprotein (anti-gp) antibody responses to zoster vaccine live (ZVL) are correlated with protection, suggesting a potential protective role for antibody. Detailed studies of antibody responses to the recombinant zoster vaccine (RZV) are provided. Methods We compared enzyme-linked immunosorbent assay–measured anti–VZV glycoproteins (anti-gp) and glycoprotein E (anti-gE) antibody levels and avidity in 159 participants randomized to RZV (n = 80) or ZVL (n = 79) recipients over 5 years after vaccination and identified predictors of antibody persistence. Results The comparison between vaccine groups showed higher anti-gE and anti-gp antibody levels after RZV than after ZVL over the 5-year study duration. RZV recipients also had higher anti-gE avidity for 5 years and higher anti-gp avidity in the first year after vaccination. Compared with prevaccination levels, RZV recipients maintained higher levels of anti-gE antibodies and avidity for 5 years, whereas ZVL recipients only maintained higher anti-gE avidity. Anti-gp antibody levels and avidity decreased to prevaccination levels or below beyond 1 year after vaccination in both groups. Independent predictors of persistence of antibody levels and avidity included vaccine type, prevaccination and peak antibody levels and avidity, prevaccination and peak cell-mediated immunity, and age. Sex or prior ZVL administration did not affect persistence. Conclusions Antibody responses and avidity were higher and more persistent in RZV than in ZVL recipients. The effect of age on antibody persistence in RZV recipients is novel. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) causes significant disease burden in older adults. MVA-BN-RSV is a novel poxvirus-vectored vaccine encoding internal and external RSV proteins. Methods In a phase 2a randomized double-blind, placebo-controlled trial, healthy participants aged 18 to 50 years received MVA-BN-RSV or placebo, then were challenged 4 weeks later with RSV-A Memphis 37b. Viral load was assessed from nasal washes. RSV symptoms were collected. Antibody titers and cellular markers were assessed before and after vaccination and challenge. Results After receiving MVA-BN-RSV or placebo, 31 and 32 participants, respectively, were challenged. Viral load areas under the curve from nasal washes were lower (P =.017) for MVA-BN-RSV (median = 0.00) than placebo (median = 49.05). Total symptom scores also were lower (median = 2.50 and 27.00, respectively; P =.004). Vaccine efficacy against symptomatic, laboratory-confirmed or culture-confirmed infection was 79.3% to 88.5% (P =.022 and.013). Serum immunoglobulin A and G titers increased approximately 4-fold after MVA-BN-RSV vaccination. Interferon-γ–producing cells increased 4- to 6-fold after MVA-BN-RSV in response to stimulation with the encoded RSV internal antigens. Injection site pain occurred more frequently with MVA-BN-RSV. No serious adverse events were attributed to vaccination. Conclusions MVA-BN-RSV vaccination resulted in lower viral load and symptom scores, fewer confirmed infections, and induced humoral and cellular responses. Clinical Trials Registration NCT04752644. [ABSTRACT FROM AUTHOR]

Background Maternal breastmilk is a source of pre- and pro-biotics that impact neonatal gut microbiota colonization. Because oral rotavirus vaccines (ORVs) are administered at a time when infants are often breastfed, breastmilk microbiota composition may have a direct or indirect influence on vaccine take and immunogenicity. Methods Using standardized methods across sites, we compared breastmilk microbiota composition in relation to geographic location and ORV response in cohorts prospectively followed from birth to 18 weeks of age in India (n = 307), Malawi (n = 119), and the United Kingdom ([UK] n = 60). Results Breastmilk microbiota diversity was higher in India and Malawi than the UK across 3 longitudinal samples spanning weeks of life 1 to 13. Dominant taxa such as Streptococcus and Staphylococcus were consistent across cohorts; however, significant geographic differences were observed in the prevalence and abundance of common and rare genera throughout follow up. No consistent associations were identified between breastmilk microbiota composition and ORV outcomes including seroconversion, vaccine shedding after dose 1, and postvaccination rotavirus-specific immunoglobulin A level. Conclusions Our findings suggest that breastmilk microbiota composition may not be a key factor in shaping trends in ORV response within or between countries. [ABSTRACT FROM AUTHOR]

We compared neutralizing antibody responses to BA.4/5, BQ.1.1, XBB, and XBB.1.5 Omicron severe acute respiratory syndrome coronavirus 2 variants after a bivalent or ancestral coronavirus disease 2019 (COVID-19) messenger RNA booster vaccine or postvaccination infection. We found that the bivalent booster elicited moderately high antibody titers against BA.4/5 that were approximately 2-fold higher against all Omicron variants than titers elicited by the monovalent booster. The bivalent booster elicited low but similar titers against both XBB and XBB.1.5 variants. These findings inform risk assessments for future COVID-19 vaccine recommendations and suggest that updated COVID-19 vaccines containing matched vaccine antigens to circulating divergent variants may be needed. [ABSTRACT FROM AUTHOR]

Background We aimed to estimate vaccine effectiveness against infection (VE-infection) and against further transmission (VE-infectiousness) in a household setting during Delta and Omicron. Knowing these effects can aid policy makers in deciding which groups to prioritize for vaccination. Methods Participants with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test were asked about coronavirus disease 2019 (COVID-19) vaccination status and SARS-CoV-2 testing of their household members 1 month later. VE-infection and VE-infectiousness were estimated using generalized estimating equation logistic regression adjusting for age, vaccination status, calendar week, and household size. Results A total of 3399 questionnaires concerning 4105 household members were included. During the Delta period, VE-infection and VE-infectiousness of primary series were 47% (95% confidence interval [CI], −27% to 78%) and 70% (95% CI, 28% to 87%), respectively. During the Omicron period, VE-infection was −36% (95% CI, −88% to 1%) for primary series and −28% (95% CI, −77% to 7%) for booster vaccination. VE-infectiousness was 45% (95% CI, −14% to 74%) for primary series and 64% (95% CI, 31% to 82%) for booster vaccination. Conclusions Our study shows that COVID-19 vaccination is effective against infection with SARS-CoV-2 Delta and against infectiousness of SARS-CoV-2 Delta and Omicron. Estimation of VE against infection with SARS-CoV-2 Omicron was limited by several factors. Our results support booster vaccination for those in close contact with vulnerable people to prevent transmission. [ABSTRACT FROM AUTHOR]

Approximately 3% of US adults are immunocompromised and less capable of fighting infections such as SARS-CoV-2 (the causative agent of COVID-19). Individuals may be immunocompromised for reasons related to an underlying medical condition or to immunomodulatory therapies that alter the immune response. In general, vaccination with mRNA–based vaccines is effective at reducing COVID-19–associated hospitalization and death among immunocompromised populations, particularly after 3 or more doses. However, the immunocompromised population is heterogeneous, with COVID-19 vaccine-elicited immune responses and risk for severe COVID-19 existing on a continuum. Therefore, understanding the impact of vaccination and the complexity of immune responses across heterogeneous immunocompromised individuals is essential for guiding effective vaccination regimens including additional (booster) doses. In this article, we provide an overview of the immunocompromised population and the burden of disease attributable to COVID-19, while discussing key opportunities and challenges of vaccinating immunocompromised individuals. [ABSTRACT FROM AUTHOR]

Background China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. Methods This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. Results There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test–positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. Conclusions Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection. [ABSTRACT FROM AUTHOR]

Background Following historically low influenza activity during the 2020–2021 season, the United States saw an increase in influenza circulating during the 2021–2022 season. Most viruses belonged to the influenza A(H3N2) 3C.2a1b 2a.2 subclade. Methods We conducted a test-negative case-control analysis among adults ≥18 years of age at 3 sites within the VISION Network. Encounters included emergency department/urgent care (ED/UC) visits or hospitalizations with ≥1 acute respiratory illness (ARI) discharge diagnosis codes and molecular testing for influenza. Vaccine effectiveness (VE) was calculated by comparing the odds of influenza vaccination ≥14 days before the encounter date between influenza-positive cases (type A) and influenza-negative and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders. Results In total, 86 732 ED/UC ARI-associated encounters (7696 [9%] cases) and 16 805 hospitalized ARI-associated encounters (649 [4%] cases) were included. VE against influenza-associated ED/UC encounters was 25% (95% confidence interval (CI), 20%–29%) and 25% (95% CI, 11%–37%) against influenza-associated hospitalizations. VE against ED/UC encounters was lower in adults ≥65 years of age (7%; 95% CI, −5% to 17%) or with immunocompromising conditions (4%; 95% CI, −45% to 36%). Conclusions During an influenza A(H3N2)-predominant influenza season, modest VE was observed. These findings highlight the need for improved vaccines, particularly for A(H3N2) viruses that are historically associated with lower VE. [ABSTRACT FROM AUTHOR]

Background Data on cellular immune responses in persons with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection following vaccination are limited. The evaluation of these patients with SARS-CoV-2 breakthrough infections may provide insight into how vaccinations limit the escalation of deleterious host inflammatory responses. Methods We conducted a prospective study of peripheral blood cellular immune responses to SARS-CoV-2 infection in 21 vaccinated patients, all with mild disease, and 97 unvaccinated patients stratified based on disease severity. Results We enrolled 118 persons (aged 50 years [SD 14.5 years], 52 women) with SARS-CoV-2 infection. Compared to unvaccinated patients, vaccinated patients with breakthrough infections had a higher percentage of antigen-presenting monocytes (HLA-DR+), mature monocytes (CD83+), functionally competent T cells (CD127+), and mature neutrophils (CD10+); and lower percentages of activated T cells (CD38+), activated neutrophils (CD64+), and immature B cells (CD127+CD19+). These differences widened with increased disease severity in unvaccinated patients. Longitudinal analysis showed that cellular activation decreased over time but persisted in unvaccinated patients with mild disease at 8-month follow-up. Conclusions Patients with SARS-CoV-2 breakthrough infections exhibit cellular immune responses that limit the progression of inflammatory responses and suggest mechanisms by which vaccination limits disease severity. These data may have implications for developing more effective vaccines and therapies. Clinical Trials Registration. NCT04401449. [ABSTRACT FROM AUTHOR]

Background Real-world evidence of human papillomavirus (HPV) vaccine effectiveness (VE) against longitudinal outcomes is lacking among gay, bisexual, and other men who have sex with men (GBM). We compared 12-month incidence and persistence of anal HPV infection between vaccinated and unvaccinated GBM. Methods We recruited GBM aged 16–30 years in Montreal, Toronto, and Vancouver, Canada, from 2017 to 2019. Participants were followed over a median of 12 months (interquartile range, 12–13 months). Participants self-reported HPV vaccination and self-collected anal specimens for HPV DNA testing. We calculated prevalence ratios (PR) for 12-month cumulative incidence and persistence with ≥1 quadrivalent vaccine type (HPV 6/11/16/18) between vaccinated (≥1 dose at baseline) and unvaccinated participants using a propensity score-weighted, modified Poisson regression. Results Among 248 participants, 109 (44.0%) were vaccinated at baseline, of whom 62.6% received 3 doses. PRs for HPV 6/11/16/18 were 0.56 (95% confidence interval [CI],.24–1.31) for cumulative incidence and 0.53 (95% CI,.25–1.14) for persistence. PRs were 0.23 (95% CI,.05–1.03) and 0.08 (95% CI,.01–.59) for incidence and persistence, respectively, among participants who received their first dose at age ≤23 years and 0.15 (95% CI,.03–.68) and 0.12 (95% CI,.03–.54) among participants who were sexually active for ≤5 years before vaccination. Conclusions Findings support national recommendations for HPV vaccination at younger ages or soon after sexual debut. [ABSTRACT FROM AUTHOR]

Background Two- and 3-dose BNT162b2 vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including Delta and Omicron variants, was assessed among adolescents in Canada, where first and second doses were spaced longer than the manufacturer-specified 3-week interval. Methods Test-negative design estimated VE against laboratory-confirmed SARS-CoV-2 infection ≥14 days after vaccination among 12–17-year-olds in Quebec and British Columbia, Canada, between 5 September 2021 and 30 April 2022 (epidemiological weeks 36–17). VE was explored by the interval between first and second doses, time since the second dose, and with a third dose. Results The VE against Delta was ≥90% until at least 5 months after the second dose. The VE against Omicron decreased from about 65%–75% at 2–3 weeks to ≤50% by the third month after vaccination, restored to approximately 65% by a third dose. Although confidence intervals overlapped, VE against Omicron was about 5%–7% higher (absolute) when first and second doses were spaced ≥8 versus 3–4 weeks apart. Conclusions In adolescents, 2 BNT162b2 doses provided strong and sustained protection against Delta but reduced and rapidly waning VE against Omicron. A longer interval between first and second doses and a third dose marginally improved Omicron protection. [ABSTRACT FROM AUTHOR]

We estimated the effectiveness of a fourth dose of mRNA COVID-19 vaccine against Omicron infections and severe outcomes over time among long-term care residents in Ontario, Canada. Fourth doses provide additional protection against Omicron-related outcomes, but the protection wanes over time, with more waning seen against infection than severe outcomes. [ABSTRACT FROM AUTHOR]

Background Immune protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be induced by natural infection or vaccination or both. Interaction between vaccine-induced immunity and naturally acquired immunity at the population level has been understudied. Methods We used regression models to evaluate whether the impact of coronavirus disease 2019 (COVID-19) vaccines differed across states with different levels of naturally acquired immunity from March 2021 to April 2022 in the United States. Analysis was conducted for 3 evaluation periods separately (Alpha, Delta, and Omicron waves). As a proxy for the proportion of the population with naturally acquired immunity, we used either the reported seroprevalence or the estimated proportion of the population ever infected in each state. Results COVID-19 mortality decreased as coverage of ≥1 dose increased among people ≥65 years of age, and this effect did not vary by seroprevalence or proportion of the total population ever infected. Seroprevalence and proportion ever infected were not associated with COVID-19 mortality, after controlling for vaccine coverage. These findings were consistent in all evaluation periods. Conclusions COVID-19 vaccination was associated with a sustained reduction in mortality at state level during the Alpha, Delta, and Omicron periods. The effect did not vary by naturally acquired immunity. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 immunity has declined with subsequent waves and accrual of viral mutations. In vitro studies raise concern for immune escape by BA.4/BA.5, and a study in Qatar showed moderate protection, but these findings have yet to be reproduced. Methods This retrospective cohort study included individuals tested for coronavirus disease 2019 by polymerase chain reaction during Delta or BA.1/BA.2 and retested during BA.4/BA.5. The preventable fraction (PF) was calculated as ratio of the infection to the hospitalization rate for initially positive patients divided by the ratio for initially negative patients, stratified by age and adjusted for age, sex, comorbid conditions, and vaccination using logistic regression. Results A total of 20 987 patients met inclusion criteria. Prior Delta infection provided no protection against BA.4/BA.5 infection (adjusted PF, 11.9% [95% confidence interval,.8%–21.8%]); P =.04) and minimal protection against hospitalization (10.7% [4.9%–21.7%]; P =.003). In adjusted models, prior BA.1/BA.2 infection provided 45.9% (95% confidence interval, 36.2%–54.1%; P <.001) protection against BA.4/BA.5 reinfection and 18.8% (10.3%–28.3%; (P <.001) protection against hospitalization. Up-to-date vaccination provided modest protection against reinfection with BA.4/BA.5 and hospitalization. Conclusions Prior infection with BA.1/BA.2 and up-to-date vaccination provided modest protection against infection with BA.4/BA.5 and hospitalization, while prior Delta infection provided minimal protection against hospitalization and none against infection. [ABSTRACT FROM AUTHOR]

Background: The impact variant-specific immune evasion and waning protection have on declining COVID-19 vaccine effectiveness remains unclear. Using whole-genome-sequencing (WGS), we examined the contribution of these factors on the decline observed following the introduction of the Delta variant. Further, we evaluated the utility of calendar-period-based classification as an alternative to WGS.Methods: We conducted a test-negative-case-control study among people who received SARS-CoV-2 RT-PCR testing in the Yale New Haven Health System between April 1 and August 24, 2021. Variant classification was performed using WGS and calendar-period.Results: Overall, 2,029 cases (RT-PCR positive, sequenced samples [infections]) and 343,985 controls (negative RT-PCRs) were included. VE 14-89 days after 2nd dose was significantly higher against WGS-classified Alpha-infection (84.4%, CI: 75.6-90.0%) than Delta-infection (68.9%, CI: 58.0-77.1%, p-value = 0.013). The odds of WGS-classified Delta-infection were significantly higher 90-149 than 14-89 days after 2nd dose (p-value = 0.003). VE estimates against calendar-period-classified infections approximated estimates against WGS-classified infections, however, calendar-period-based classification was subject to outcome misclassification (35%: Alpha-period, 4%: Delta-period).Conclusions: Both waning protection and variant-specific immune evasion contributed to the lower effectiveness. While VE estimates against calendar-period-classified infections mirrored those against WGS-classified infections, our analysis highlights the need for WGS when variants are co-circulating and misclassification is likely. [ABSTRACT FROM AUTHOR]

Background Evidence is accumulating of coronavirus disease 2019 (COVID-19) vaccine effectiveness among persons with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods We evaluated the effect against incident SARS-CoV-2 infection of (1) prior infection without vaccination, (2) vaccination (2 doses of Pfizer-BioNTech COVID-19 vaccine) without prior infection, and (3) vaccination after prior infection, all compared with unvaccinated persons without prior infection. We included long-term care facility staff in New York City aged <65 years with weekly SARS-CoV-2 testing from 21 January to 5 June 2021. Test results were obtained from state-mandated laboratory reporting. Vaccination status was obtained from the Citywide Immunization Registry. Cox proportional hazards models adjusted for confounding with inverse probability of treatment weights. Results Compared with unvaccinated persons without prior infection, incident SARS-CoV-2 infection risk was lower in all groups: 54.6% (95% confidence interval, 38.0%–66.8%) lower among unvaccinated, previously infected persons; 80.0% (67.6%–87.7%) lower among fully vaccinated persons without prior infection; and 82.4% (70.8%–89.3%) lower among persons fully vaccinated after prior infection. Conclusions Two doses of Pfizer-BioNTech COVID-19 vaccine reduced SARS-CoV-2 infection risk by ≥80% and, for those with prior infection, increased protection from prior infection alone. These findings support recommendations that all eligible persons, regardless of prior infection, be vaccinated against COVID-19. [ABSTRACT FROM AUTHOR]

Background There are discrepant observations on the severity of tick-borne encephalitis (TBE) in vaccinated persons. We, therefore, analyzed the occurrence of severe and mild disease in hospitalized vaccinated and nonvaccinated patients with TBE and determined the field effectiveness (FE) of vaccination against these forms of disease. Methods The study covered all patients hospitalized with TBE in Austria from 2000 to 2018. Clinical diagnoses in vaccinated and age- and sex-matched nonvaccinated patients were compared in a nested case-control study. FE was calculated based on vaccination coverage and incidences in the nonvaccinated and vaccinated population. Results Of 1545 patients hospitalized with TBE, 206 were vaccinated. In those, a higher proportion of severe TBE was observed, especially in children. FE was high in all age groups and against all forms of disease. The higher proportion of severe TBE can be explained by a lower FE against severe than against mild disease, a difference especially pronounced in children (FE, 82.7% for severe vs 94.7% for mild disease). Conclusions The FE of TBE vaccination is excellent. The observed higher proportion of severe disease in vaccinated persons with TBE does not reflect a higher risk associated with vaccination but is rather due to a somewhat lower FE against severe TBE. Because this effect was more pronounced in children, we recommend adapting the immunization schedule. [ABSTRACT FROM AUTHOR]

The most effective measure to induce protection from influenza is vaccination. Thus, yearly vaccination is recommended, which, together with infections, establishes diverse repertoires of B cells, antibodies, and T cells. We examined the impact of this accumulated immunity on human responses in adults to split, subunit, and recombinant protein-based influenza vaccines. Enzyme-linked immunosorbent assay (ELISA) assays, to quantify serum antibodies, and peptide-stimulated CD4 T-cell cytokine ELISpots revealed that preexisting levels of hemagglutinin (HA)-specific antibodies were negatively associated with gains in antibody postvaccination, while preexisting levels of CD4 T cells were negatively correlated with vaccine-induced expansion of CD4 T cells. These patterns were seen independently of the vaccine formulation administered and the subjects' influenza vaccine history. Thus, although memory CD4 T cells and serum antibodies consist of components that can enhance vaccine responses, on balance, the accumulated immunity specific for influenza A H1 and H3 proteins is associated with diminished future responses. [ABSTRACT FROM AUTHOR]

When first approved, many hoped that the SARS-CoV-2 vaccine would provide long-term protection after a primary series. Waning of immunity and continued appearance of new variants has made booster inoculations necessary. The process is becoming increasingly similar to that used for annual updating of the influenza vaccine. The similarity has become even more apparent with selection of BA.4/BA.5 as the Omicron strain of the updated bivalent (Original + Omicron) Covid-19 vaccines. It is hoped that, if Covid-19 develops winter seasonality, SARS-CoV-2 vaccines will require only annual review to determine if updates are necessary. Recommendations on whom should receive the booster would be based on conditions at that time. [ABSTRACT FROM AUTHOR]

In their first season of vaccination, young children are recommended 2 doses of influenza vaccine, but a 2-dose schedule might be difficult to implement in many countries. Within a cohort study of 742 children aged 6 to <24 months in Managua, Nicaragua, this study estimated effectiveness of partial vaccination from 3 to 9 months postvaccination. Vaccine effectiveness was 74% (95% confidence interval [CI], 24%–91%) within 3 months and 55% (95% CI, 10%–77%) within 4 months. There was not significant protection beyond 5 months. Partial vaccination might confer some benefits but should be followed by a second dose. [ABSTRACT FROM AUTHOR]

Background: Understanding how booster vaccination can prevent moderate and severe illness without hospitalization is crucial to evaluate the full advantage of mRNA boosters.Methods: We followed 85 801 participants (aged 31-81 years) in 2 large population-based cohorts during the Omicron BA.1/2 wave. Information on home testing, PCR testing, and symptoms of coronavirus disease 2019 (COVID-19) was extracted from biweekly questionnaires covering the period 12 January 2022 to 7 April 2022. Vaccination status and data on previous SARS-CoV-2 infection were obtained from national registries. Cox regression was used to estimate the effectiveness of booster vaccination compared to receipt of 2-dose primary series >130 days previously.Results: The effectiveness of booster vaccination increased with increasing severity of COVID-19 and decreased with time since booster vaccination. The effectiveness against severe COVID-19 was reduced from 80.9% shortly after booster vaccination to 63.4% in the period >90 days after vaccination. There was hardly any effect against mild COVID-19. The effectiveness tended to be lower among subjects aged ≥60 years than those aged <50 years.Conclusions: This is the first population-based study to evaluate booster effectiveness against self-reported mild, moderate, and severe COVID-19. Our findings contribute valuable information on duration of protection and thus timing of additional booster vaccinations. [ABSTRACT FROM AUTHOR]

Background: Despite the advent of safe and effective coronavirus disease 2019 vaccines, pervasive inequities in global vaccination persist.Methods: We projected health benefits and donor costs of delivering vaccines for up to 60% of the population in 91 low- and middle-income countries (LMICs). We modeled a highly contagious (Re at model start, 1.7), low-virulence (infection fatality ratio [IFR], 0.32%) "Omicron-like" variant and a similarly contagious "severe" variant (IFR, 0.59%) over 360 days, accounting for country-specific age structure and healthcare capacity. Costs included vaccination startup (US$630 million) and per-person procurement and delivery (US$12.46/person vaccinated).Results: In the Omicron-like scenario, increasing current vaccination coverage to achieve at least 15% in each of the 91 LMICs would prevent 11 million new infections and 120 000 deaths, at a cost of US$0.95 billion, for an incremental cost-effectiveness ratio (ICER) of US$670/year of life saved (YLS). Increases in vaccination coverage to 60% would additionally prevent up to 68 million infections and 160 000 deaths, with ICERs Conclusions: Funding expanded COVID-19 vaccine delivery in LMICs would save hundreds of thousands of lives, be similarly or more cost-effective than other donor-funded global aid programs, and improve health equity. [ABSTRACT FROM AUTHOR]

Background: An effective dengue vaccine should ideally induce broadly neutralizing antibody (nAb) responses against all 4 dengue virus (DENV) serotypes.Methods: We characterized the specificity and breadth of the nAb response to TAK-003, a live-attenuated tetravalent dengue vaccine, in serum samples from phase 2 and 3 clinical trials.Results: Microneutralization tests using postvaccination serum showed comparable neutralization against diverse DENV-1-4 genotypes. Reporter virus particle neutralization assays after depletion of anti-DENV-2 nAbs demonstrated that the nAb response to DENV-1, -3, and -4 comprises both type-specific (TS) and cross-reactive (CR) nAbs.Conclusions: Therefore, TAK-003 induces broad tetravalent TS and CR nAb responses. [ABSTRACT FROM AUTHOR]

Decision making about vaccination and boosting schedules for coronavirus disease 2019 (COVID-19) hinges on reliable methods for evaluating the longevity of vaccine protection. We show that modeling of protection as a piecewise linear function of time since vaccination for the log hazard ratio of the vaccine effect provides more reliable estimates of vaccine effectiveness at the end of an observation period and also detects plateaus in protective effectiveness more reliably than the standard method of estimating a constant vaccine effect over each time period. This approach will be useful for analyzing data pertaining to COVID-19 vaccines and other vaccines for which rapid and reliable understanding of vaccine effectiveness over time is desired. [ABSTRACT FROM AUTHOR]

To inform public health policy, it is critical to monitor COVID-19 vaccine effectiveness (VE), including against acquiring infection. We estimated VE using self-reported vaccination in a retrospective cohort of repeat blood donors who donated during the first half of 2021, demonstrating a viable approach for monitoring of VE via serological surveillance. Using Poisson regression, we estimated an overall VE of 88.8% (95% CI: 86.2-91.1), adjusted for demographic covariates and variable baseline risk. Time since first reporting vaccination, age, race-ethnicity, region, and calendar time were statistically significant predictors of incident infection. [ABSTRACT FROM AUTHOR]

Background: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades immunity conferred by vaccines and previous infections.Methods: We used a Cox proportional hazards model and a logistic regression on individual-level population-wide data from the Czech Republic to estimate risks of infection and hospitalization, including severe states.Results: A recent (≤2 months) full vaccination reached vaccine effectiveness (VE) of 43% (95% confidence interval [CI], 42%-44%) against infection by Omicron compared to 73% (95% CI, 72%-74%) against Delta. A recent booster increased VE to 56% (95% CI, 55%-56%) against Omicron infection compared to 90% (95% CI, 90%-91%) for Delta. The VE against Omicron hospitalization of a recent full vaccination was 45% (95% 95% CI, 29%-57%), with a recent booster 87% (95% CI, 84%-88%). The VE against the need for oxygen therapy due to Omicron was 57% (95% CI, 32%-72%) for recent vaccination, 90% (95% CI, 87%-92%) for a recent booster. Postinfection protection against Omicron hospitalization declined from 68% (95% CI, 68%-69%) at ≤6 months to 13% (95% CI, 11%-14%) at >6 months after a previous infection. The odds ratios for Omicron relative to Delta were 0.36 (95% CI, .34-.38) for hospitalization, 0.24 (95% CI, .22-.26) for oxygen, and 0.24 (95% CI, .21-.28) for intensive care unit admission.Conclusions: Recent vaccination still brings substantial protection against severe outcome for Omicron. [ABSTRACT FROM AUTHOR]

Background The study objective was to evaluate 2- and 3-dose coronavirus disease 2019 (COVID-19) mRNA vaccine effectiveness (VE) in preventing COVID-19 hospitalization among adult solid organ transplant (SOT) recipients. Methods We conducted a 21-site case-control analysis of 10 425 adults hospitalized in March to December 2021. Cases were hospitalized with COVID-19; controls were hospitalized for an alternative diagnosis (severe acute respiratory syndrome coronavirus 2-negative). Participants were classified as follows: SOT recipient (n = 440), other immunocompromising condition (n = 1684), or immunocompetent (n = 8301). The VE against COVID-19-associated hospitalization was calculated as 1-adjusted odds ratio of prior vaccination among cases compared with controls. Results Among SOT recipients, VE was 29% (95% confidence interval [CI], −19% to 58%) for 2 doses and 77% (95% CI, 48% to 90%) for 3 doses. Among patients with other immunocompromising conditions, VE was 72% (95% CI, 64% to 79%) for 2 doses and 92% (95% CI, 85% to 95%) for 3 doses. Among immunocompetent patients, VE was 88% (95% CI, 87% to 90%) for 2 doses and 96% (95% CI, 83% to 99%) for 3 doses. Conclusions Effectiveness of COVID-19 mRNA vaccines was lower for SOT recipients than immunocompetent adults and those with other immunocompromising conditions. Among SOT recipients, vaccination with 3 doses of an mRNA vaccine led to substantially greater protection than 2 doses. [ABSTRACT FROM AUTHOR]

Evaluating the impact of public health investments in vaccination programs is crucial for ensuring their efficiency and effectiveness. Vaccine effectiveness (VE) studies, such as those using the test-negative design (TND), are commonly used to confirm the impact of vaccines and to guide future improvements. The TND, favored for its simplicity and cost efficiency, mitigates biases common in other epidemiological study designs. However, its validity can be compromised by inconsistent symptom definitions and retrospective data application. Here we summarize recent findings that highlight the need to address correlated vaccination behaviors when estimating VE, that suggest using negative control variables to reduce confounding, and that recommend accounting for prior infection history in VE studies to improve accuracy and reliability. These insights are important for refining VE estimation methods., (© 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 In British Columbia, Canada, most adults 50–69 years old became eligible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in April 2021, with chimpanzee adenoviral vectored vaccine (ChAdOx1) restricted to ≥55-year-olds and second doses deferred ≥6 weeks to optimize single-dose coverage. Methods Among adults 50–69 years old, single-dose messenger RNA (mRNA) and ChAdOx1 vaccine effectiveness (VE) against SARS-CoV-2 infection and hospitalization, including variant-specific, was assessed by test-negative design between 4 April and 2 October 2021. Results Single-dose VE included 11 861 cases and 99 544 controls. Median of postvaccination follow-up was 32 days (interquartile range, 15–52 days). Alpha, Gamma, and Delta variants comprised 23%, 18%, and 56%, respectively, of genetically characterized viruses. At 21–55 days postvaccination, single-dose mRNA and ChAdOx1 VE (95% confidence interval [CI]) was 74% (71%–76%) and 59% (53%–65%) against any infection and 86% (80%–90%) and 94% (85%–97%) against hospitalization, respectively. VE (95% CI) was similar against Alpha and Gamma infections for mRNA (80% [76%–84%] and 80% [75%–84%], respectively) and ChAdOx1 (69% [60%–76%] and 66% [56%–73%], respectively). mRNA VE was lower at 63% (95% CI, 56%–69%) against Delta but 85% (95% CI, 71%–92%) against Delta-associated hospitalization (nonestimable for ChAdOx1). Conclusions A single mRNA or ChAdOx1 vaccine dose gave important protection against SARS-CoV-2, including early variants of concern. ChAdOx1 VE was lower against infection, but 1 dose of either vaccine reduced the hospitalization risk by >85% to at least 8 weeks postvaccination. Findings inform program options, including longer dosing intervals. [ABSTRACT FROM AUTHOR]