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BACKGROUND: The interpretation of relative vaccine effectiveness (rVE) of improved influenza vaccines is complex. Estimation of burden averted is useful to contextualise their potential impact across different seasons. For the population aged under 65 years in Australia, this study estimated the additional morbidity and mortality that could be averted using improved influenza vaccines. METHODS: We used observed, season-specific (2015-2019) influenza notification and influenza-coded hospitalisation frequencies and published modelled estimates of influenza-associated hospitalisations and deaths that occurred under the prevailing influenza vaccination coverage scenario. After back-calculating to the estimated burden in the population without vaccination, we applied published standard influenza vaccine effectiveness and coverage estimates to calculate the burden potentially averted by standard and improved influenza vaccines. A plausible range of rVE values were used, assuming 50% coverage. RESULTS: The percentage point difference in absolute vaccine effectiveness (VE) of an improved vaccine compared to a standard vaccine is directly proportional to its rVE and inversely proportional to the effectiveness of the standard vaccine. The incremental burden averted by an improved vaccine is a function of both its difference in absolute VE and the severity of the influenza season. Assuming an rVE of 15% with 50% coverage, the improved vaccine was estimated to additionally avert 1517 to 12,641 influenza notifications, 287 to 1311 influenza-coded hospitalisations and 9 to 33 modelled all-cause influenza deaths per year compared to the standard vaccine. CONCLUSIONS: Improved vaccines can have substantial clinical and population impact, particularly when the effectiveness of standard vaccines is low, and burden is high.

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. [ABSTRACT FROM AUTHOR]

The unprecedented global impact of the 2019 coronavirus disease (COVID-19) has necessitated a comprehensive understanding of its transmission dynamics and control measures. In this study, we present a detailed analysis of a COVID-19 vaccination model tailored to the context of Bangladesh, incorporating dual-dose vaccination strategies. By employing qualitative and bifurcation analysis techniques, we investigate the equilibrium points, effective reproduction number (R0), and critical thresholds that influence the prevalence and control of COVID-19 in the region. Our findings reveal insights into the effectiveness of vaccination programs and provide a framework for developing targeted control plans. Through a rigorous examination of model parameters and sensitivity analysis, we identify key factors driving COVID-19 transmission dynamics, emphasizing the significance of vaccination rates and other critical parameters. The validation of our model against real-world data underscores its utility in informing evidence-based decision-making for managing the COVID-19 pandemic in Bangladesh and beyond. [ABSTRACT FROM AUTHOR]

Chikungunya virus is an emerging mosquito-borne alphavirus that causes febrile illness and arthritic disease. Chikungunya virus is endemic in 110 countries and the World Health Organization estimates that it has caused more than 2 million cases of crippling acute and chronic arthritis globally since it re-emerged in 2005. Chikungunya virus outbreaks have occurred in Africa, Asia, Indian Ocean islands, South Pacific islands, Europe, and the Americas. Until recently, no specific countermeasures to prevent or treat chikungunya disease were available. To address this need, multiple vaccines are in human trials. These vaccines use messenger RNA-lipid nanoparticles, inactivated virus, and viral vector approaches, with a live-attenuated vaccine VLA1553 and a virus-like particle PXVX0317 in phase III testing. In November 2023, the US Food and Drug Administration (FDA) approved the VLA1553 live-attenuated vaccine, which is marketed as IXCHIQ. In June 2024, Health Canada approved IXCHIQ, and in July 2024, IXCHIQ was approved by the European Commission. On August 13, 2024, the US FDA granted priority review for PXVX0317. The European Medicine Agency is considering accelerated assessment review of PXVX0317, with potential for approval by both agencies in 2025. In this review, we summarize published data from pre-clinical and clinical trials for the IXCHIQ and PXVX0317 vaccines. We also discuss unanswered questions including potential impacts of pre-existing chikungunya virus immunity on vaccine safety and immunogenicity, whether long-term immunity can be achieved, safety in children, pregnant, and immunocompromised individuals, and vaccine efficacy in people with previous exposure to other emerging alphaviruses in addition to chikungunya virus. [ABSTRACT FROM AUTHOR]

This study examines the factors influencing COVID-19 vaccination intentions among Chinese residents over the age of 60, with a focus on the mediating roles of Health Beliefs and Cues to Vaccination Action in the relationship between vaccine knowledge and vaccination intentions. We conducted a cross-sectional online survey involving 1,305 participants from Southwest China. Multiple logistic regression analysis identified potential determinants of vaccination intention, including socioeconomic characteristics, knowledge, health beliefs, and cues to vaccination action. Furthermore, mediation analysis using the causal mediation analysis method explored the mediating effects within the knowledge-to-intention pathway. Vaccination intention and its related factors: among the 1212 elderly people included in the study, 92.9% expressed willingness to receive the COVID-19 vaccine. Main factors influencing their vaccination willingness included Residency (urban vs. rural, OR = 0.47, p < 0.01), Age (75 + vs. others, OR = 0.41, p < 0.05), Marital status (OR = 0.36, p < 0.01), Occupation (business/service vs. others, OR = 0.33, p < 0.05), Awareness of vaccine effectiveness (OR = 1.23, p < 0.01), Cues to vaccination action (OR = 1.31, p < 0.01) and COVID-19 related knowledge (OR = 1.06, p < 0.01). The analysis revealed two significant mediators—Health Beliefs and Cues to Vaccination Action. These mediators (p<0.05 for both natural indirect effect and natural direct effect) acted along two key pathways: (1) From Knowledge of COVID-19 to Health Beliefs to Vaccination Intention: Natural Direct Effects (NDE) ranged from 0.012 to 0.016, with Natural Indirect Effects (NIE) from 0.001 to 0.003, indicating that mediators accounted for 4% to 18% of the total effect. (2) From Knowledge of COVID-19 to Cues of Vaccination Action to Vaccination Intention: NDE ranged from 0.012 to 0.016 and NIE from 0.002 to 0.003, with mediators accounting for 9% to 20% of the effect. The intention to vaccinate against COVID-19 among older adults varies significantly based on socioeconomic and health belief factors. The study identifies health beliefs and cues to action not only as direct contributors but also as crucial mediators in the pathway from knowledge to vaccination intention among older individuals. These findings can extend our understanding of the impact of sociodemographic factors and health beliefs on the COVID-19 vaccination willingness among older adults. [ABSTRACT FROM AUTHOR]

In Kenya, influenza virus circulates year-round, raising questions about optimum strategies for vaccination. Given national interest in introducing influenza vaccination for young children 6-23 months of age, we modeled total influenza-associated illnesses (inclusive of hospitalizations, outpatient illnesses, and non-medically attended illnesses) averted by multiple potential vaccination strategies: yearround versus seasonal-campaign vaccination, and vaccination starting in April (Southern Hemisphere influenza vaccine availability) versus October (Northern Hemisphere availability). We modeled average vaccine effectiveness of 50% and annual vaccination coverage of 60%. In the introduction year, year-round vaccination averted 6,410 total illnesses when introduced in October and 7,202 illnesses when introduced in April, whereas seasonal-campaign vaccination averted 10,236 (October) to 11,612 (April) illnesses. In the year after introduction, both strategies averted comparable numbers of illnesses (10,831-10,868 for year-round, 10,175-11,282 for campaign). Campaign-style vaccination would likely have a greater effect during initial pediatric influenza vaccine introduction in Kenya; however, either strategy could achieve similar longer-term effects. [ABSTRACT FROM AUTHOR]

Introduction: The evidence regarding the effectiveness of Lanzhou Lamb Rotavirus Vaccine (LLR) and RotaTeq (RV5) against gastroenteritis (RVGE) caused by emerging genotypes in Chinese children remains limited. Methods: We conducted a test-negative case–control study using gastroenteritis surveillance data from four cities (2020–2023) in Guangdong Province, China. Children aged 2 months to 5 years hospitalized with acute gastroenteritis were enrolled. Cases were rotavirus-positive; controls were rotavirus-negative. Vaccine effectiveness (VE) was estimated using multivariable logistic regressions. Results: Among 2650 children, 218 (8.2%) were rotavirus-positive, predominantly G8P[8]. Also, 1543 (58.23%) children were unvaccinated, while 632 (23.85%) and 475 (17.92%) received at least one dose of RV5 and LLR, respectively. Adjusted RV5 VE against any RVGE severity was 51.7% [95% confidence interval (CI) − 58.1–85.3%]) for one dose, 37.6% (95% CI − 58.5–75.4%) for two doses, and 64.1% (95% CI 38.0–79.2%) for three doses. For LLR, VE against any RVGE severity was 38.7% (95% CI 5.7–60.2%) for one dose, 74.6% (95% CI 35.3–90.0%) for two doses, and 58.8% (95% CI − 217.6–94.6%) for three doses. Against severe RVGE, RV5 VE was 67.2% (95% CI − 144.7–95.6%) for one dose, 74.0% (95% CI − 92.1–96.5%) for two doses, and 86.6% (95% CI 56.8–95.9%) for three doses. For LLR, VE against severe RVGE was 57.7% (95% CI 20.3–77.6%) for one dose, 73.4% (95% CI 11.9–92.0%) for two doses, and − 27.8% (95% CI − 949.7–84.4%) for three doses. Conclusions: Both RV5 and LLR provided protection against RVGE, including the emerging G8P[8] genotype. Three doses of RV5 offered strong protection, while two doses of LLR also appeared to be an effective strategy against rotavirus infection. Plain Language Summary: Rotavirus is a common cause of severe diarrhea in young children, and vaccines are crucial in preventing this illness. This study looked at how well two rotavirus vaccines, Lanzhou Lamb Rotavirus Vaccine (LLR) and RotaTeq (RV5), protect children against rotavirus gastroenteritis (RVGE), including infections caused by a new strain called G8P[8]. We analyzed data from children aged 2 months to 5 years who were hospitalized between 2020 and 2023. We compared children who tested positive for rotavirus (cases) with those who tested negative (controls) to determine how well the vaccines worked. Our results showed that both RV5 and LLR vaccines provided protection against RVGE. For RV5, three doses provided strong protection, while for LLR, two doses provided good protection. Against severe RVGE, three doses of RV5 were effective, while two doses of LLR also showed good protection. [ABSTRACT FROM AUTHOR]

A single-dose dengue vaccine that protects individuals across a wide age range and regardless of dengue serostatus is an unmet need. We assessed the safety and efficacy of the live, attenuated, tetravalent Butantan-dengue vaccine (Butantan-DV) in adults, adolescents, and children. We previously reported the primary and secondary efficacy and safety endpoints in the initial 2 years of follow-up. Here we report the results through an extended follow-up period, with an average of 3·7 years of follow-up. In this double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil, healthy participants (aged 2–59 years) who had not previously received a dengue vaccine were enrolled and randomly assigned 2:1 (stratified by age 18–59 years, 7–17 years, and 2–6 years) using a central electronic randomisation system to receive 0·5 mL of Butantan-DV (containing approximately 103 plaque-forming units of each of the four vaccine virus strains) or placebo, administered subcutaneously. Syringes containing vaccine or placebo were prepared by an unmasked trial pharmacist who was not involved in any subsequent participant assessments; other site staff and the participants remained unaware of the group allocations. Vaccine efficacy was calculated with the accrual of virologically confirmed dengue (VCD) cases (by RT-PCR) at least 28 days after vaccination up until the cutoff (at least 2 years of follow-up from the last participant enrolled). The primary endpoint was vaccine efficacy against VCD after day 28 by any dengue virus (DENV) serotype regardless of dengue serostatus at baseline in the per-protocol population. The primary and secondary safety endpoints up until day 21 were previously reported; secondary safety endpoints include the frequency of unsolicited vaccine-related adverse events after day 22. Safety analyses were done on all participants as treated. This trial is registered with ClinicalTrials.gov (NCT02406729) and is ongoing. Of 16 363 participants assessed for eligibility, 16 235 were randomly assigned between Feb 22, 2016, and July 5, 2019, and received single-dose Butantan-DV (10 259 participants) or placebo (5976 participants). 16 162 participants (Butantan-DV n=10 215; placebo n=5947) were included in the per-protocol population and 16 235 (Butantan-DV n=10 259; placebo n=5976) in the safety population. At the data cutoff (July 13, 2021), participants had 2–5 years of follow-up (mean 3·7 years [SD 1·0], median 4·0 years [IQR 3·2–4·5]). 356 VCD cases were captured through the follow-up (128 in the vaccine group and 228 in the placebo group). Vaccine efficacy against VCD caused by any DENV serotype was 67·3% (95% CI 59·4–73·9); cases caused by DENV-3 or DENV-4 were not observed. The proportions of participants who had serious adverse events were similar between treatment groups (637 [6·2%] in the vaccine group and 395 [6·6%] in the placebo group) up until the cutoff. A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus. Instituto Butantan and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. For the Spanish and Portuguese translations of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Rift Valley fever virus, a pathogen to ruminants, camelids, and humans, is an emerging mosquito-borne bunyavirus currently endemic to Africa and the Arabian Peninsula. Although animals are primarily infected via mosquito bites, humans mainly become infected following contact with infected tissues or fluids of infected animals. There is an urgent need for adequate countermeasures, especially for humans, because effective therapeutics or vaccines are not yet available. Here we assessed the safety, tolerability, and immunogenicity of a next-generation, four-segmented, live-attenuated vaccine candidate, referred to as hRVFV-4s, in humans. A first-in-human, single-centre, randomised, double-blind, placebo-controlled trial was done in Belgium in which a single dose of hRVFV-4s was administered to healthy volunteers aged 18–45 years. Participants were randomly assigned using an interactive web response system. The study population encompassed 75 participants naive to Rift Valley fever virus infection, divided over three dosage groups (cohorts) of 25 participants each. All participants were followed up until 6 months. Using a staggered dose escalating approach, 20 individuals of each cohort were injected in the deltoid muscle of the non-dominant arm with either 104 (low dose), 105 (medium dose), or 106 (high dose) of 50% tissue culture infectious dose of hRVFV-4s as based on animal data, and five individuals per cohort received formulation buffer as a placebo. Primary outcome measures in the intention-to-treat population were adverse events and tolerability. Secondary outcome measures were vaccine-induced viraemia, vaccine virus shedding, Rift Valley fever virus nucleocapsid antibody responses (with ELISA), and neutralising antibody titres. Furthermore, exploratory objectives included the assessment of cellular immune responses by ELISpot. The trial was registered with the EU Clinical Trials Register, 2022-501460-17-00. Between August and December, 2022, all 75 participants were vaccinated. No serious adverse events or vaccine-related severe adverse events were reported. Pain at the injection site (51 [85%] of 60 participants) was most frequently reported as solicited local adverse event, and headache (28 [47%] of 60) and fatigue (28 [47%] of 60) as solicited systemic adverse events in the active group. No vaccine virus RNA was detected in any of the blood, saliva, urine, or semen samples. Rift Valley fever virus nucleocapsid antibody responses were detected in most participants who were vaccinated with hRVFV-4s (43 [72%] of 60 on day 14) irrespective of the administered dose. In contrast, a clear dose–response relationship was observed for neutralising antibodies on day 28 with four (20%) of 20 participants responding in the low-dose group, 13 (65%) of 20 responding in the medium-dose group, and all participants (20 [100%] of 20) responding in the high-dose group. Consistent with the antibody responses, cellular immune responses against the nucleocapsid protein were detected in all dose groups, whereas a more dose-dependent response was observed for the Gn and Gc surface glycoproteins. Neutralising antibody titres declined over time, whereas nucleocapsid antibody responses remained relatively stable for at least 6 months. The hRVFV-4s vaccine showed a high safety profile and excellent tolerability across all tested dose regimens, eliciting robust immune responses, particularly with the high-dose administration. The findings strongly support further clinical development of this candidate vaccine for human use. The Coalition for Epidemic Preparedness Innovations with support from the EU Horizon 2020 programme. [ABSTRACT FROM AUTHOR]

HIV type 1 (HIV-1) remains a global health concern, with the greatest burden in sub-Saharan Africa. Despite 40 years of research, no vaccine candidate has shown durable and protective efficacy against HIV-1 acquisition. Although pre-exposure prophylaxis in groups with high vulnerability can be very effective, barriers to its use, such as perceived low acquisition risk, fear of stigma, and concerns about side-effects, remain. Thus, a population-based approach, such as an HIV-1 vaccine, is needed. The current study aimed to evaluate the efficacy and safety of a heterologous HIV-1 vaccine regimen, consisting of a tetravalent mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) and aluminium phosphate-adjuvanted clade C glycoprotein (gp) 140, in young women at risk of acquiring HIV-1 in southern Africa. This randomised, double-blind, phase 2b study enrolled sexually active women without HIV-1 or HIV-2 aged 18–35 years at 23 clinical research sites in Malawi, Mozambique, South Africa, Zambia, and Zimbabwe. Participants were centrally randomly assigned (1:1) to receive intramuscular injections of vaccine or saline placebo in stratified permuted blocks via an interactive web response system. Study participants, study site personnel (except those with primary responsibility for study vaccine preparation and dispensing), and investigators were masked to treatment group allocation. The vaccine regimen consisted of Ad26.Mos4.HIV administered at months 0 and 3 followed by Ad26.Mos4.HIV administered concurrently with aluminium phosphate-adjuvanted clade C gp140 at months 6 and 12. The primary efficacy outcome was vaccine efficacy in preventing laboratory-confirmed HIV-1 acquisition diagnosed between visits at month 7 and month 24 after the first vaccination (VE[7–24]) in the per-protocol population, which included participants who had not acquired HIV-1 4 weeks after the third vaccination, received all planned vaccinations at the first three vaccination visits within the protocol-specified windows, and had no major protocol deviations that could affect vaccine efficacy. Primary safety outcomes were assessed in randomly assigned participants who received one study injection or more based on the actual injection received. The primary safety endpoints were the incidences of unsolicited adverse events (AEs), solicited local and systemic AEs, serious AEs, AEs of special interest, and AEs leading to discontinuation of vaccination. This trial is registered with ClinicalTrials.gov , NCT03060629 , and is complete. Between Nov 3, 2017, and June 30, 2019, 2654 women were randomly assigned, of whom 2636 women (median age of 23 years [IQR 20–25]) were enrolled and received at least one study injection (1313 assigned vaccine, 1323 placebo; 1317 received vaccine, 1319 placebo). Analysis of the primary efficacy outcome in the per-protocol cohort included 1080 women in the vaccine group and 1108 women in the placebo group; the incidence of HIV-1 acquisition per 100 person-years over months 7–24 after the first vaccination was 3·38 (95% CI 2·54–4·41) in the vaccine group and 3·94 (3·04–5·03) in the placebo group, with an estimated VE(7–24) of 14·10% (95% CI –22·00 to 39·51; p=0·40). There were no serious unsolicited AEs, AEs of special interest, or deaths related to the study vaccine. In the vaccine group, 663 (50·3%) of 1317 participants had grade 1 or 2 solicited local AEs and ten (0·8%) of 1317 participants had grade 3 or 4 solicited local AEs. In the placebo group, 305 (23·1%) of 1319 participants had grade 1 or 2 solicited local AEs and three (0·2%) of 1319 participants had grade 3 or 4 solicited local AEs. 863 (65·5%) of 1317 participants in the vaccine group had grade 1 or 2 solicited systemic AEs and 34 (2·6%) of 1317 participants had grade 3 or 4 solicited systemic AEs. 763 (57·8%) of 1319 participants in the placebo group had grade 1 or 2 solicited systemic AEs and 20 (1·5%) of 1319 participants had grade 3 or 4 solicited systemic AEs. Overall, three (0·2%) of 1317 participants in the vaccine group and three (0·2%) of 1319 participants in the placebo group discontinued vaccination due to an unsolicited AE, and three (0·2%) of 1317 participants in the vaccine group and one (0·1%) of 1319 participants in the placebo group discontinued vaccination due to a solicited AE. The heterologous Ad26.Mos4.HIV and clade C gp140 vaccine regimen was safe and well tolerated but did not show efficacy in preventing HIV-1 acquisition in a population of young women in southern Africa at risk of HIV-1. Division of AIDS at the National Institute of Allergy and Infectious Diseases through the HIV Vaccine Trials Network, Bill & Melinda Gates Foundation, Janssen Vaccines & Prevention, US Army Medical Materiel Development Activity, and Ragon Institute. [ABSTRACT FROM AUTHOR]

Recent advances in clinical passive immunotherapy have provided compelling evidence that eliminating amyloid-β (Aβ) slows cognitive decline in Alzheimer's disease (AD). However, the modest benefits and side effects observed in clinical trials indicate that current immunotherapy therapy is not a panacea, highlighting the need for a deeper understanding of AD mechanisms and the significance of early intervention through optimized immunotherapy or immunoprevention. This review focuses on the centrality of Aβ pathology in AD and summarizes recent clinical progress in passive and active immunotherapies targeting Aβ, discussing their lessons and failures to inform future anti-Aβ biotherapeutics design. Various delivery strategies to optimize Aβ-targeting immunotherapies are outlined, highlighting their benefits and drawbacks in overcoming challenges such as poor stability and limited tissue accessibility of anti-Aβ biotherapeutics. Additionally, the perspectives and challenges of immunotherapy and immunoprevention targeting Aβ are concluded in the end, aiming to guide the development of next-generation anti-Aβ immunotherapeutic agents towards improved efficacy and safety. We review the recent advances in amyloid-β-targeting passive and active immunotherapy, and summarize versatile delivery strategies to guide the development of next-generation antibodies and vaccines with improved efficacy and safety. [Display omitted] [ABSTRACT FROM AUTHOR]

Four‐finger threadfin, Eleutheronema tetradactylum farming in southern Taiwan has been facing disease problems caused by Streptococcus iniae since 2018. The development of a vaccine against infectious S. iniae in the cultured threadfin industry is necessary. Thus, this study aimed to examine the efficacy of threadfin immunized formalin‐killed cells (FKC) from S. iniae GSI‐111 for 42 days post‐vaccination (dpv) using two doses of FKC alone (a booster at 14 dpv) as group A, and FKC mixed with ISA763A adjuvant using a single dose as group B or double doses as group C. Immunoglobulin (Ig)‐M was purified from threadfin, and rabbit anti‐threadfin IgM polyclonal antibodies were used to detect antibody level in immunized fish; the vaccinated group A displayed higher levels at 3 dpv and all vaccinated treatments demonstrated high antibody levels between 14 and 42 dpv. All vaccine groups showed significantly higher values of lysozyme activity at 42 dpv compared with the control group; the vaccinated A group peaked at 14 dpv. The expression profiles of pro‐inflammatory and immune‐related genes, TNF‐α, IL‐12A, and C2 were upregulated at 3 dpv, while CD8A and chemokine receptor CXCR4 were upregulated at 42 dpv. Finally, the threadfins were challenged with S. iniae at 42 dpv. The average relative percent survival was 96% for vaccination A and B treatments, and 100% for vaccination C treatment. In summary, this study demonstrated that FKC vaccines whether formulated with an adjuvant could stimulate immune response and effective protect threadfins against S. iniae infection. [ABSTRACT FROM AUTHOR]

Studying inflammatory responses induced by vaccination can contribute to a more detailed understanding of underlying immune mechanisms in lumpfish (Cyclopterus lumpus). Tissue samples from lumpfish intraperitoneally immunized with a divalent oil‐adjuvanted vaccine (Aeromonas salmonicida and Vibrio salmonicida) at water temperatures of 5, 10, and 15°C were collected at 630 day degrees and 18 weeks post injection. The relative amount of secretory and membrane‐bound immunoglobulin M (IgM) gene transcripts in the head kidney was determined by qPCR. Vaccine‐induced inflammatory lesions were assessed on histological sections of abdominal pancreatic/intestinal tissue from vaccinated fish in all three temperature groups. Inflammatory cells forming dense aggregations in lesions showed proliferative activity, many of which were identified as eosinophilic‐granulocyte‐like cells. IgM+ cells were scattered in inflammatory tissue dominated by connective tissue, showing no difference in numbers between lesions from fish vaccinated at 5, 10, and 15°C. Relative gene expression analysis of secretory and membrane‐bound IgM revealed low overall expression in the head kidney of vaccinated fish at both 630 day‐degrees and 18 weeks post injection. The results of this study indicate that the vaccine stimulated prolonged local inflammatory responses at the injection site, which were not influenced by temperature. [ABSTRACT FROM AUTHOR]

The Strep Easy Kit, a bio‐enrichment dual ICG‐strip test, is a diagnostic tool designed for the detection of Streptococcus agalactiae, an important pathogenic bacterium in tilapia farming. The kit can simultaneously identify two different serotypes of S. agalactiae, serotype Ia and serotype III. This capability is crucial for the collection of valuable epidemiological data and facilitates strategic planning for effective vaccine development and deployment. The Strep Easy Kit consists of two main steps: pathogen enrichment and pathogen detection. The enrichment step increases the concentration of bacteria so that the bacterial load is raised to the level reliably detectable by the subsequent ICG strip test. This is achieved by incubating the fish samples in a suitable liquid medium under specified temperature and time conditions. The second step involves the use of the dual‐ICG strip test. This strip test consists of two monoclonal antibodies and one polyclonal antibody that are specific to S. agalactiae and can distinguish between S. agalactiae serotype Ia and S. agalactiae serotype III. This dual capability enables the ICG strip test to simultaneously detect both serotypes of S. agalactiae in a single test kit. The detection limit of the test kit, which consists of a dual ICG‐Strip test combined with an enrichment step, is 100 CFU/mL. The kit can be used to detect S. agalactiae in both live and dead fish samples, making it versatile for various testing scenarios. The test results obtained using the Strep Easy Kit have shown a 94.4% correlation with the standard method (Thai Agricultural Standard; TAS 10453‐2010), with 90.2% sensitivity and 100% specificity. Significant advantages of the Strep Easy Kit lie in its simplicity and portability, allowing farmers to perform the test by themselves and on‐site. This makes it a practical and accessible tool for the tilapia farming industry. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is still an urgent global public health problem. Notably, mucosal‐associated invariant T (MAIT) cells play an important role in early anti‐TB immune response. Targeted control of them may be an effective method to improve vaccine efficacy and TB treatment. However, the biology and signal regulation mechanisms of MAIT cells in TB patients are still poorly understood. Previous studies have been limited by the lack of reagents to specifically identify MAIT cells. In addition, the use of alternative markers may subsume non‐MAIT cell into MAIT cell populations. In this study, the human MR1 tetramer which can specifically identify MAIT cells was used to further explore the effect and mechanism of MAIT cells in anti‐TB immune response. Our results showed that the tetramer+ MAIT cells in peripheral blood of TB patients were mainly CD8+ or CD4−CD8− cells, and very few were CD4+ cells. After BCG infecting autologous antigen‐presenting cells, MAIT cells in patients produced significantly higher levels of cytokines, lysis and proliferation compared with healthy controls. After suppression of mTORC1 by the mTORC1‐specific inhibitor rapamycin, the immune response of MAIT cells in patients was significantly reduced. This study demonstrates that peripheral blood tetramer+ MAIT cells from TB patients have significant anti‐TB immune effect, which is regulated by mTORC1. This could provide ideas and potential therapeutic targets for the development of novel anti‐TB immunotherapy. [ABSTRACT FROM AUTHOR]

• Interleukin-1β (IL-1β) increased after influenza vaccine but not placebo injection. • Greater IL-1β increase after vaccine was linked to more intergroup bias. • IL-1β change was negatively associated with evaluation of Latina applicant's resume. • IL-1β change was positively associated with ethnocentrism. • Findings suggest that working while sick may contribute to disparities in hiring. Situational factors can increase people's vulnerability to intergroup bias, including prejudicial attitudes, negative stereotyping, and discrimination. We proposed that increases in inflammatory activity that coincide with acute illness may represent a hitherto unstudied situational factor that increases intergroup bias. The current study experimentally manipulated increases in inflammatory activity by administering the seasonal influenza vaccine or a saline placebo. We quantified inflammatory activity by assessing change in salivary pro-inflammatory cytokines and assessed intergroup bias using a resume evaluation task and self-reported ethnocentrism. Primary analyses focused on a subsample of 117 participants who provided high quality data; robustness analyses included various permutations of lower quality participants. Findings revealed that changes in the cytokine interleukin-1β (IL-1β) in response to the vaccine were associated with greater intergroup bias. Among participants who received the vaccine, IL-1β change was negatively associated with evaluation of a Latina (but not a White woman) applicant's competency and recommended starting salary. Moreover, IL-1β change was positively associated with ethnocentrism. Overall, results provide support for the hypothesis that acute illness, via the mechanistic role of inflammatory cytokines, affects social cognition in ways that can increase intergroup bias. [ABSTRACT FROM AUTHOR]

The multi drug-resistant Neisseria gonorrhoeae has been classified by the World Health Organisation (WHO) as a high-priority global public health problem. This underlines the need for better understanding of the transmission dynamics and proposing an optimal intervention strategy to control the disease. In this article, a deterministic mathematical model for the transmission dynamics of gonorrhoea as an antibiotic resistant disease in a population with an imperfect vaccination is proposed and analysed. The model incorporates the classes of vaccinated individuals and individuals equipped with self protection interventions to reduce antibiotic resistant cases. The threshold parameter R 0 , the basic reproduction number, for the analysis of the model is calculated. In the given setting, the model exhibits a backward bifurcation for R 0 < 1. However, if the efficacy of the vaccine is 100% without a waning effect, the model is shown to be without a backward bifurcation and the disease-free equilibrium is globally asymptotically stable whenever R 0 < 1. The global sensitivity analysis of the model to variations in parameter values is also performed to determine the most influential parameters on the disease transmission. Moreover, the optimal control analysis of the full model is presented and the optimal intervention strategies are proposed. The proposed intervention strategies are shown to be able to control the disease within a relatively shorter period of time. Finally, numerical experiments are presented to support the theoretical analysis of the model. • Imperfect vaccination is not helpful to eradicate the disease from the population. • Awareness campaign about the antibiotic resistant strain can reduce the transmission of the disease. • Sensitive parameters for the transmission dynamics of the disease are identified. • With the use of the optimal control analysis, cost effective intervention measures are proposed. [ABSTRACT FROM AUTHOR]

Vaccination is a cornerstone of canine preventive healthcare and one of the most cost-effective ways of maintaining a dog's health, longevity, and quality of life. Canine vaccination also serves a public health function by forming a barrier against several zoonotic diseases affecting dogs and humans. Canine vaccines are broadly categorized as containing core and noncore immunizing antigens, with administration recommendations based on assessment of individual patient risk factors. The guidelines include a comprehensive table listing canine core and noncore vaccines and a recommended vaccination and revaccination schedule for each vaccine. The guidelines explain the relevance of different vaccine formulations, including those containing modified-live virus, inactivated, and recombinant immunizing agents. Factors that potentially affect vaccine efficacy are addressed, including the patient's prevaccination immune status and vaccine duration of immunity. Because animal shelters are one of the most challenging environments for prevention and control of infectious diseases, the guidelines also provide recommendations for vaccination of dogs presented at or housed in animal shelters, including the appropriate response to an infectious disease outbreak in the shelter setting. The guidelines explain how practitioners can interpret a patient's serological status, including maternally derived antibody titers, as indicators of immune status and suitability for vaccination. Other topics covered include factors associated with postvaccination adverse events, vaccine storage and handling to preserve product efficacy, interpreting product labeling to ensure proper vaccine use, and using client education and healthcare team training to raise awareness of the importance of vaccinations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Improving acceptance of the COVID-19 vaccine among nursing students is an important strategy for both preventing infection and building public confidence in the vaccine. OBJECTIVE: The aim of this study was to describe the views of intern nursing students on the COVID-19 vaccine and to evaluate their experiences in the COVID-19 vaccination unit. METHODS: This was a phenomenological qualitative study with a descriptive design. The 46 intern nursing students included in this study were all trained in the COVID-19 vaccination unit. The data was collected at focus group interviews conducted during June 2021 and October 2021. RESULTS: The mean age of intern nursing students was 22.78±0.91. From the focus group interviews, two themes were identified regarding the views of intern nursing students on the COVID-19 vaccine and their experiences in the COVID-19 vaccination unit: Theme 1. Positive views; Theme 2. Negative views. Intern nursing students described that they trust the COVID-19 vaccine and believe in its protection. Intern nursing students who performed their clinical practices in COVID-19 vaccination unit stated that they realized their responsibilities toward patients and the community. CONCLUSIONS: From the INSs' point of view, confidence in the vaccine, responsibility towards patients, their families and the community, and VU practice experience, the health risk associated with COVID-19 positively affected their decision to be vaccinated against COVID-19. The participation of intern nursing students in clinical practice during the pandemic influenced both intern nursing students and population in terms of the uptake of COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

To end the HIV epidemic, there is need for targeted strategies to reduce HIV incidence for those most vulnerable, including an HIV vaccine. This study seeks to understand the perceptions that non-PrEP using gay and bisexual men and other men who have sex with men (GBMSM) have about a potential HIV vaccine, while contextualizing their perspectives within the context of heightened vaccine hesitancy that has emerged since the COVID-19 pandemic. Between March and May of 2022, GBMSM (N = 20) participated in in-depth interviews, which assessed their perceptions about an HIV vaccine. Interviews were analysed using a codebook approach to thematic analysis. We oversampled for those unvaccinated against COVID-19 as a proxy for vaccine hesitation. Participants expressed a range of enthusiastic support, cautious optimism and skepticism when presented with the possibility of an HIV vaccine. Factors that drove willingness to receive an HIV vaccine included community-oriented altruism, individualized risk-benefit assessment, and/or the perception that a vaccine could provide a beneficial shift in sexual experiences. Participants also expressed hesitations about receiving an HIV vaccine, including concerns about potential side-effects and efficacy, as well as mistrust in the vaccine development process. Notably, participants often evaluated the vaccine in comparison to PrEP and condoms. Participants offered specific insights into information they would like to receive about an HIV and where/how they would like to receive it. Our findings can help inform future HIV vaccine implementation efforts by offering insights into the factors that motivate and deter GBMSM to receive an HIV vaccine. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Since its first isolation from migratory birds in Egypt in 2016, highly pathogenic avian influenza (HPAI) H5N8 has caused several outbreaks among domestic poultry in various areas of the country affecting poultry health and production systems. However, the genetic and biological properties of the H5N8 HPAI viruses have not been fully elucidated yet. In this study, we aimed to monitor the evolution of circulating H5N8 viruses and identify the pathogenicity and mammalian adaptation in vitro and in vivo. Three H5N8 HPAI viruses were used in this study and were isolated in 2021–2022 from poultry and wild birds during our routine surveillance. RNA extracts were subjected to full genome sequencing. Genetic, phylogenetic, and antigenic analyses were performed to assess viral characteristics and similarities to previously isolated viruses. Phylogenetic analysis showed that the hemagglutinin genes of the three isolates belonged to clade 2.3.4.4b and grouped with the 2019 viruses from G3 with high similarity to Russian and European lineages. Multiple basic amino acids were observed at cleavage sites in the hemagglutinin proteins of the H5N8 isolates, indicating high pathogenicity. In addition, several mutations associated with increased virulence and polymerase activity in mammals were observed. Growth kinetics assays showed that the H5N8 isolate is capable of replicating efficiently in mammalian cells lines. In vivo studies were conducted in SPF chickens (White Leghorn), mice, and hamsters to compare the virological characteristics of the 2022 H5N8 isolates with previous H5N8 viruses isolated in 2016 from the first introduction. The H5N8 viruses caused lethal infection in all tested chickens and transmitted by direct contact. However, we showed that the 2016 H5N8 virus causes a higher mortality in chickens compared to 2022 H5N8 virus. Moreover, the 2022 virus can replicate efficiently in hamsters and mice without preadaptation causing systemic infection. These findings underscore the need for continued surveillance of H5 viruses to identify circulating strains, determine the commercial vaccine's effectiveness, and identify zoonotic potential. [ABSTRACT FROM AUTHOR]

Infants with congenital heart disease (CHD) often undergo thymectomy during corrective cardiac surgery (CCS). The long‐term immunological effects remain controversial, with concerns regarding increased susceptibility to infections, allergies, autoimmunity due to compromised immune tolerance mechanisms. This study aims to elucidate the long‐term immunological effects of early thymectomy. We enrolled 22 patients who underwent thymectomy in infancy and were followed up in the Pediatric Allergy and Immunology Clinic at Marmara University. We performed demographic characteristics and detailed immunological evaluation, including immunoglobulins, vaccine responses, lymphocyte subset analyses, upregulation, proliferation of T cells and T‐cell receptor excision circles (TRECs). Sixteen patients had a history of infection, including six serious infections, all in the first year. Lymphopenia was observed in 27% of patients, with a significant decrease in naive CD4+ and recent thymic emigrant T cells counts and an increase in the proportion of memory T‐cells, indicating premature immune senescence. Low levels of IgG, IgA and IgM were found in 36%, 40% and 22% of patients respectively. Vaccine responses were positive in 90% of patients. TREC levels were low in all 10 patients analysed. Seven of nine patients had normal proliferation. Twenty‐two percent of patients had allergic disease, and autoimmunity was not observed. Early thymectomy leads to permanent immunological changes that are indicative of early immunosenescence. It is recommended to preserve thymic tissue during surgery and requires long‐term follow‐up in terms of findings such as allergy and autoimmunity as well as infections due to impaired immune tolerance mechanisms. [ABSTRACT FROM AUTHOR]

Host immunity is central to the virus's spread dynamics, which is significantly influenced by vaccination and prior infection experiences. In this work, we analyzed the co‐evolution of SARS‐CoV‐2 mutation, angiotensin‐converting enzyme 2 (ACE2) receptor binding, and neutralizing antibody (NAb) responses across various variants in 822 human and mice vaccinated with different non‐Omicron and Omicron vaccines is analyzed. The link between vaccine efficacy and vaccine type, dosing, and post‐vaccination duration is revealed. The classification of immune protection against non‐Omicron and Omicron variants is co‐evolved with genetic mutations and vaccination. Additionally, a model, the Prevalence Score (P‐Score) is introduced, which surpasses previous algorithm‐based models in predicting the potential prevalence of new variants in vaccinated populations. The hybrid vaccination combining the wild‐type (WT) inactivated vaccine with the Omicron BA.4/5 mRNA vaccine may provide broad protection against both non‐Omicron variants and Omicron variants, albeit with EG.5.1 still posing a risk. In conclusion, these findings enhance understanding of population immunity variations and provide valuable insights for future vaccine development and public health strategies. [ABSTRACT FROM AUTHOR]

This article is a summary of the first AGS Symposium entitled “Update on Vaccination Strategies for Older Adults: Matching the Approach to the Individual and the Care Setting.” Given declines in host defenses and immune function with aging, vaccinations play a pivotal role in fortifying older adults against preventable infections, resulting diseases, disability, and death. Current guidelines generally list recommendations applicable for an average older adult of a given chronological age. However, growing evidence indicates that heterogeneity in terms of factors as varied as biological sex, frailty, functional status, and multimorbidity may impact vaccine responses and clinical outcomes. As a result, clinicians will increasingly need to take these additional factors into consideration as they seek to improve outcomes through improved targeting of such aging‐related heterogeneity. Moreover, efforts at protecting older citizens through vaccination must also include strategies to overcome barriers to the adoption of vaccine recommendations in varied settings including long‐term care. This 2023 AGS Plenary Symposium sought to commence a broader dialogue across AGS and beyond on optimizing vaccinations for older adults, ensuring not only extended lifespans but also healthier and more active lives. This report is not a systematic review, and thus should not be considered comprehensive. [ABSTRACT FROM AUTHOR]

The RTS, S/AS01 vaccine is a significant milestone in advancing malaria control, especially in Africa, where the heavy burden of this disease is prevalent. The objective of this study is to discuss the effectiveness and utilization of the RTS, S/AS01 vaccine in Africa while simultaneously addressing the gaps and associated issues. We also explore briefly the R21/Matrix-M vaccines recommended by the World Health Organization (WHO) for children aged five months and older. Essential considerations include but are not limited to the vaccine's effectiveness, implementation challenges, available funding sources, public acceptance, and compatibility with various conventional prevention methods for malaria, like insecticide-coated bed nets and antimalarial medicines. This paper also examines the global practices for integrating vaccines into public health systems and policies while emphasizing sustainable and equitable approaches. By drawing from the lessons learned from the implementations of pilot programs as well as early adoption of the RTS, S/AS01 malaria vaccine, this perspective study tries to identify the key factors that may enhance the impact of the vaccine in the fight against malaria and significantly contribute to the vision of complete eradication the disease. Further research needs to be carried out regarding the efficacy and duration of protection of the RTS, S/AS01 vaccine. [ABSTRACT FROM AUTHOR]

Natural adjuvants have recently garnered interest in the field of vaccinology as their immunostimulatory effects. In this study, we aimed to investigate the potential use of Peyssonnelia caulifera (PC), a marine alga, as a natural adjuvant for an inactivated split A/Puerto Rico/8/1934 H1N1 influenza vaccine (sPR8) in a murine model. We administered PC-adjuvanted vaccines to a murine model via intramuscular prime and boost vaccinations, and subsequently analyzed the induced immunological responses, particularly the production of antigen-specific IgG1 and IgG2a antibodies, memory T and B cell responses, and the protective efficacy against a lethal viral infection. PC extract significantly bolstered the vaccine efficacy, demonstrating balanced Th1/Th2 responses, increased memory T and B cell activities, and improved protection against viral infection. Notably, within 3 days post-vaccination, the PC adjuvant stimulated activation markers on dendritic cells (DCs) and macrophages at the inguinal lymph nodes (ILN), emphasizing its immunostimulatory capabilities. Furthermore, the safety profile of PC was confirmed, showing minimal local inflammation and no significant adverse effects post-vaccination. These findings contribute to our understanding of the immunomodulatory properties of natural adjuvants and suggest the promising roles of natural adjuvants in the development of more effective vaccines for infectious diseases. [ABSTRACT FROM AUTHOR]

Vaccination plays a crucial role in preventing and controlling SARS-CoV-2 infections as well as their associated adverse outcomes. But there is a notable lack of research on the effectiveness of COVID-19 vaccination in children, particularly those young preterm-born children, who are more vulnerable to severe outcomes from SARS-CoV-2 infection. We aimed to determine the effect of vaccination with inactivated vaccines BBIBP-CorV and CoronaVac on symptomatic COVID-19 infection and related symptoms in preterm-born children aged 3–7 years after relaxation of the COVID-19 prevention and control measures in December 2022 in China. We performed a retrospective cohort study involving 242 preterm-born children aged 3–7 years and the data were collected in March 2023. Logistic regression models and modified Poisson regression models combined with entropy balancing were used to explore the associations of vaccination against SARS-CoV-2 with symptomatic COVID-19, specific symptoms, and persistent symptoms one month after recovery from COVID-19. Of the 242 recruited preterm-born children, 156 (64.5%) were vaccinated with inactivated vaccines BBIBP‐CorV and CoronaVac. After entropy balancing, the covariates were balanced between the vaccinated and the unvaccinated groups, with standardized mean difference < 0.001. Vaccination with the said SARS-CoV-2 vaccines lowered the risk of developing symptomatic COVID-19 in preterm-born children (risk ratio [RR] = 0.783; 95% confidence interval [CI]: (0.711, 0.861). Likewise, COVID-19 vaccination was associated with a decline in the risk of pneumonia (odds ratio [OR] = 0.318; 95% CI 0.110, 0.913), fever (RR = 0.710; 95% CI 0.635, 0.794), high fever (RR = 0.542; 95% CI 0.297, 0.988), sore throat (OR = 0.304; 95% CI 0.139, 0.664), and persistent symptoms (RR = 0.425; 95% CI 0.182, 0.993). Immunization with inactivated vaccines BBIBP‐CorV and CoronaVac provides protection against symptomatic COVID-19 for preterm-born children 3–7 years. [ABSTRACT FROM AUTHOR]

During of COVID-19 pandemic, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has continuously evolved, resulting in the emergence of several new variants of concerns (VOCs) with numerous mutations. These VOCs dominate in various regions due to increased transmissibility and antibody evasion, potentially reducing vaccine effectiveness. Nonetheless, it remains uncertain whether the recent SARS-CoV-2 VOCs have the ability to circumvent the T cell immunity elicited by either COVID-19 vaccination or natural infection. To address this, we conducted in-silico analysis to examine the impact of VOC-specific mutations at the epitope level and T cell cross-reactivity with the ancestral SARS-CoV-2. According to the in-silico investigation, T cell responses triggered by immunization or prior infections still recognize the variants in spite of mutations. These variants are expected to either maintain their dominant epitope HLA patterns or bind with new HLAs, unlike the epitopes of the ancestral strain. Our findings indicate that a significant proportion of immuno-dominant CD8 + and CD4 + epitopes are conserved across all the variants, implying that existing vaccines might maintain efficacy against new variations. However, further in-vitro and in-vivo studies are needed to validate the in-silico results and fully elucidate immune sensitivities to VOCs. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant pathogen in the worldwide swine industry. The virus shows high genetic variation coupled with a broad range of virulence in pigs. Although multiple lineages of the virus have been prevalent throughout in Korea, the characteristics of lineage‐wise pathogenicity are largely unknown. Therefore, this study was designed to analyze and compare the pathogenicity of 11 representative Korean PRRSV‐2 isolates selected from PRRSV‐2 lineages circulating in Korea, NADC30‐like, VR2332‐like, and three nation‐specific lineages (lineage KOR A (LKA), lineage KOR B (LKB), and lineage KOR C (LKC)), which have been continuously prevalent in the nation. Eleven groups of pigs were experimentally infected with one Korean PRRSV‐2 isolate through four consecutive animal experiments. Body weight and body temperature were recorded during each 4‐week challenge experiment period, and virological, serological, and histopathological tests were performed on the collected samples. The data from the animal experiments were integrated into two indicators—excretion and clinical signs—through correlation and principal component analysis (PCA). Meta‐analysis was used to compare PRRSV‐2 isolates using each indicator. Based on these analyses, while L1C viruses used in this study (JB15‐N‐P31‐GB and JB15‐N‐PJ73‐GN, similar to NADC30‐like strains) exhibited low or moderate levels of excretion and clinical signs, lineage 5 (L5) or modified live vaccine (MLV)‐variant strains exhibited high levels of excretion compared to other PRRSV‐2 isolates. However, the L5 variants all caused mild clinical signs, except for JB15‐N‐PJ4‐GN, which showed the 4th highest clinical sign indicator. Among the Korean lineages (LKA, LKB, and LKC), two LKB strains (GGYC45 and JB15‐N‐PJ10‐GN) were the most virulent as they showed the highest mortality after the challenge. On the other hand, the LKA and LKC viruses displayed lower excretion indicators than L5 strains, but they had higher‐ranked clinical sign indicators than low‐virulence L5 MLV variants. In conclusion, PRRSV prevalent in Korea has diverse excretion and clinical characteristics, and certain lineage is highly pathogenic. These results will offer useful insights to prevent spread of PRRSV and improve the efficacy of vaccines in the future. [ABSTRACT FROM AUTHOR]

Two vaccination-challenge trials were performed using a commercial infectious bronchitis virus (IBV) BR1 vaccine, given alone or combined with a commercial IBV Mass vaccine against challenges with IBV M41, 793B, D388 (QX), Q1, Brasil-1 or Variant 2 challenge viruses, which includes the IB viruses that are dominant in South America. The efficacy of the vaccines against the challenge viruses was investigated by determination of the ciliary activity of the tracheal epithelium after challenge. The level of protection induced by the IBV BR1 vaccine alone against the six IBV challenge strains, of which five were of heterologous genotypes, varied from 50% to 100% with an average of 80%. The level of protection induced by the combination of the IBV BR1 and IBV Mass vaccines against the six IBV challenge strains, of which four were of heterologous genotypes, varied from 80% to 100% with an average of 92%. Vaccination with IBV BR1 alone provided a high level of protection against most tested challenge viruses, though the combination of IBV BR1 and IBV Mass was more consistent, showing less variation and compliance with the criterium mentioned in the European Pharmacopoeia 10th edition (at least 80% protection) for all tested challenge viruses. These trials show that vaccination with a combination of IBV BR1 and IBV Mass vaccines provides high levels of protection against the circulating IBV strains in South America. [ABSTRACT FROM AUTHOR]

Effective vaccines against Salmonella Typhi, targeting the Vi capsular polysaccharide, have been developed and are being introduced into routine immunization in endemic countries. Vi conjugated vaccines are also being tested in new multi-component vaccine formulations. Simple, high-throughput and cost-effective assays to quantify Vi-specific IgG in clinical sera are needed. In this study we present the development and qualification of a new anti-Vi ELISA with continuous readout, which expresses results as ELISA Unit/mL (EU/mL). We have qualified the assay in terms of precision, linearity and specificity, demonstrating performance in line with a commercially available anti-Vi ELISA. We have also calibrated the assay against the 16/138 anti-Vi international standard and established conversion factor between EU/mL and international units/mL, to allow comparability of results across studies. In summary, this newassaymet all the suitability criteria and is being used to evaluate anti-Vi responses in clinical studies. [ABSTRACT FROM AUTHOR]

RTS,S/AS01E, the first approved malaria vaccine, demonstrated moderate efficacy during the phase 3 pediatric trial. We previously investigated cell-mediated immune (CMI) responses following the primary 3-dose immunization and now report responses to the booster dose given 18 months later. Thirty CMI markers were measured by Luminex in supernatants of peripheral blood mononuclear cells from 709 children and infants after RTS,S/AS01E antigen stimulation, and their associations with malaria risk and antibodies one month post-booster and one year later were assessed. IL-2, IFN-γ, IL-17, IL-5, and IL-13 were associated with RTS,S/AS01E booster vaccination, and IL-2 responses to the circumsporozoite protein (CSP) remained higher after one year. IL-2 was associated with reduced malaria risk in one site, and IL-10 was associated with increased risk in infants. Anti-CSP IgG and IL-2 were moderately correlated one year after booster. This study highlights the moderate cell-mediated immunogenicity of the RTS,S/AS01E booster dose that aligns with partial recovery of RTS,S/AS01E vaccine efficacy. [ABSTRACT FROM AUTHOR]

This study analyzed Chest CT exams from 592 patients with SARS-CoV-2 between 2020 and 2022 using the open-source 3D Slicer software. We conducted lung segmentation and volume quantification to investigate inflated lung volume and different impairments volumes (inflammatory process and fibrosis, ground-glass opacities and the total affected lung) against SARS-CoV-2 variants (original strain, gamma, delta and omicron) during a mass vaccination campaign carried out in Botucatu/SP-Brazil (before, during, and after three doses). We aimed to verify whether these parameters (variants and vaccination) affected lung impairments. Our findings indicated that gamma variant was more detrimental than delta and omicron variants, with higher volumes in inflammatory process and fibrosis (13.78% against 9.00% and 8.90%), ground-glass opacity (31.73% against 25.81% and 29.04%) and total affected volume (45.99% against 35.26% and 38.43%), while a lower volume was observed for inflated lung volume (50.04% against 58.19% and 57.50%). The results also revealed substantial differences in pulmonary impairments between the first and the third vaccination stages. We noticed a reduction in volumes of inflammatory process and fibrosis (14.51% to 9.19%), ground-glass opacity (33.67% to 26.77%) and the total affected volume (48.60% to 36.42%), while inflated lung volume increased (48.80% to 58.12%). The study brings novelty approach and findings that enhances the understanding of variant-specific impacts on pulmonary impairments and highlights the vaccine efficacy in reducing lung damage from SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Increasing vaccination coverage was key to curbing the COVID-19 pandemic globally. However, lack of trust in the vaccine and fear of side effects in regions like the Caribbean resulted in a low uptake despite enough vaccine supply. Methods: We conducted two correlational analyses and one experiment between five sequential behaviorally informed Facebook campaigns, social media performance outcomes, and district-level vaccination data. First, we ran multivariate linear regression models to estimate the mean differences between the campaigns in (i) social media performance ("Clicks" and "Engagement") and (ii) COVID-19 vaccination uptake at the district level. "Clicks" were measured by the number of people who clicked on the respective Facebook advert and visited the official vaccination site. "Engagements" were the number of people interacting with the advert through likes and emojis. Second, we took advantage of the experimental design during one of the campaigns to analyze the differential effect of messages conveying information about the number of people reporting vaccination side effects using words ("Few"/ "Majority) and numbers ("3 out of 100 ") on social media performance. Results: The correlational analysis showed that the number of "Clicks" and "Engagement" was similar among campaigns, except for the campaign focusing on vaccines' effectiveness, which had 14.65 less clicks and 19.52 less engagements per advert (including controls and district-fixed effects) compared to the base "It's safe" campaign. Vaccination rates were highest at times coinciding with campaigns focusing on vaccination safety and effectiveness. Our experimental results showed that informational messages related to side effects that were framed using words ("Majority did not report discomfort"/ "Few persons reported discomfort") were better at generating "Clicks" compared to those using numbers ("3 out of 100 reported discomforts"). Conclusions: Facebook adverts highlighting vaccine safety had a similar level of social media performance as other campaigns, except for adverts focusing on vaccine efficacy, which performed worse. Communicating side-effect information with words instead of numbers can expand social media interest in low-uptake regions like the Caribbean. Our results serve as preliminary evidence for public health officials to encourage vaccine uptake in high-hesitancy contexts. [ABSTRACT FROM AUTHOR]

Aim: Malaria vaccine is one of the critical areas in tropical health research, considering the success recorded in other vaccine‐preventable diseases. This study is aimed at reviewing recent trends in global malaria vaccine research from 2005 to 2022. Method: A validated search strategy was undertaken to identify scientific literature on the malaria vaccine in the Scopus database. Bibliometric indicators identified include a pattern of publication growth and citations over the study period; top authors, countries, funding organizations, and journals; keywords, including different malarial parasite species, and the overall research themes. Result: A total of 6457 documents were found from 2005 to 2022, published in 160 journals/sources in 189 countries/territories. Malaria Journal published the highest number of research outputs (478, 7.4%) within the study period, and the highest number of documents (468, 7.3%) were published in 2021. There were 214,323 total citations, with 33.2 average citations per document and 167 documents' h‐index. The United States, United Kingdom, and Australia combined produced more than 60% of the publication output, with most collaboration with African countries such as Kenya. Plasmodium falciparum is the most occurring parasite species keyword (754, 11.7%), with a growing interest in Plasmodium knowlesi (30, 0.5%). Merozoite surface protein, characterization, trials, infant/children, traveler, and research/review were the six themes that emerged from the studies. Conclusion: The last one and half decades have seen a significant increase in malaria vaccine research and citations, mainly targeting vaccine development, safety, and efficacy in Africa. This necessitates more international efforts to improve the vaccines' effectiveness considering different Plasmodium species. [ABSTRACT FROM AUTHOR]

Mumps outbreaks among fully vaccinated young adults have raised questions about potential waning of immunity over time and need for a third dose of the measles, mumps, rubella (MMR) vaccine. However, there are currently limited data on real-life effectiveness of the third-dose MMR vaccine in preventing mumps. Here, we used a deterministic compartmental model to infer the effectiveness of the third-dose MMR vaccine in preventing mumps cases by analyzing the mumps outbreak that occurred at the University of Iowa between August 24, 2015, and May 13, 2016. The modeling approach further allowed us to evaluate the population-level impact of vaccination by different timing in relation to the start of the outbreak and varied coverage levels, and to account for potential sources of bias in estimating vaccine effectiveness. We found large uncertainty in vaccine effectiveness estimates; however, our models showed that early introduction of a third dose of MMR vaccine during a mumps outbreak can be effective in preventing transmission. School holidays, such as the winter break, likely played important roles in preventing mumps transmission. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Onchocerciasis (river blindness) is a debilitating tropical disease that causes significant eye and skin damage, afflicting millions worldwide. As global efforts shift from disease management to elimination, vaccines have become crucial supplementary tools. The Onchocerciasis Vaccine for Africa (TOVA) Initiative was established in 2015, to advance at least one vaccine candidate initially targeting onchocerciasis in infants and children below 5 years of age, through Phase I human trials by 2025. Notably, Ov-RAL-2 and Ov-103 antigens have shown great promise during pre-clinical development, however, the overall success rate of vaccine candidates during clinical development remains relatively low due to certain adverse effects and immunogenic limitations. This study, thus, aimed at predicting the safety and immunogenicity of Ov-RAL-2 and Ov-103 potential onchocerciasis vaccine candidates prior to clinical trials. Advanced molecular simulation models and analytical immunoinformatics algorithms were applied to predict potential adverse side effects and efficacy of these antigens in humans. The analyses revealed that both Ov-RAL-2 and Ov-103 demonstrate favourable safety profiles as toxicogenic and allergenic epitopes were found to be absent within each antigen. Also, both antigens were predicted to harbour substantial numbers of a wide range of distinct epitopes (antibodies, cytokines, and T- Cell epitopes) associated with protective immunity against onchocerciasis. In agreement, virtual vaccination simulation forecasted heightened, but sustained levels of primary and secondary protective immune responses to both vaccine candidates over time. Ov-103 was predicted to be non-camouflageable, as it lacked epitopes identical to protein sequences in the human proteome. Indeed, both antigens were able to bind with high affinity and activate the innate immune TLR4 receptor, implying efficient immune recognition. These findings suggest that Ov-RAL-2 and Ov-103 can induce sufficient protective responses through diverse humoral and cellular mechanisms. Overall, our study provides additional layer of evidence for advancing the clinical development of both vaccine candidates against onchocerciasis. [ABSTRACT FROM AUTHOR]

Hemorrhagic fever with renal syndrome (HFRS) occurs throughout Eurasia with considerable morbidity and mortality. Currently, the absence of specific treatments or effective antiviral drugs for hantavirus infection makes developing safe and effective vaccines a high priority. Here, we report the development of three novel nucleic acid vaccine candidates, mRNA, naked DNA, and DNA encapsulated in lipid nanoparticles, encoding the glycoproteins of the Hantaan virus (HTNV). To comprehensively evaluate the potential of candidate HTNV nucleic acid vaccines in preventing HFRS, we focus on evaluating their immunogenicity and efficacy in mice and comparing them with an inactivated vaccine as the benchmark. Our findings reveal that all candidate vaccines activated instant and sustained immune responses, offering comparable in vivo protective efficacy to the inactivated vaccines. Notably, compared to the inactivated vaccine, mRNA vaccine induced stronger virus-specific T-helper 1 cell immune response, while DNA-LNP elicited higher levels of neutralizing antibodies in mice. These results mark a significant step in developing nucleic acid vaccines for HTNV, suggesting that sequential immunization with DNA and mRNA vaccines could further amplify the advantages of nucleic acid vaccines. [ABSTRACT FROM AUTHOR]

Introduction: Self-antigens abnormally expressed on tumors, such as MUC1, have been targeted by therapeutic cancer vaccines. We recently assessed in two clinical trials in a preventative setting whether immunity induced with a MUC1 peptide vaccine could reduce high colon cancer risk in individuals with a history of premalignant colon adenomas. In both trials, there were immune responders and non-responders to the vaccine. Methods: Here we used PBMC pre-vaccination and 2 weeks after the first vaccine of responders and non-responders selected from both trials to identify early biomarkers of immune response involved in long-term memory generation and prevention of adenoma recurrence. We performed flow cytometry, phosflow, and differential gene expression analyses on PBMCs collected from MUC1 vaccine responders and non-responders pre-vaccination and two weeks after the first of three vaccine doses. Results: MUC1 vaccine responders had higher frequencies of CD4 cells prevaccination, increased expression of CD40L on CD8 and CD4 T-cells, and a greater increase in ICOS expression on CD8 T-cells. Differential gene expression analysis revealed that iCOSL, PI3K AKT MTOR, and B-cell signaling pathways are activated early in response to the MUC1 vaccine. We identified six specific transcripts involved in elevated antigen presentation, B-cell activation, and NFkB1 activation that were directly linked to finding antibody response at week 12. Finally, a model using these transcripts was able to predict non-responders with accuracy. Discussion: These findings suggest that individuals who can be predicted to respond to the MUC1 vaccine, and potentially other vaccines, have greater readiness in all immune compartments to present and respond to antigens. Predictive biomarkers of MUC1 vaccine response may lead to more effective vaccines tailored to individuals with high risk for cancer but with varying immune fitness. [ABSTRACT FROM AUTHOR]

Introduction: Solid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear. Methods: We investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination. Results: We corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti-spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2-producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion. Discussion: Our study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients. [ABSTRACT FROM AUTHOR]

A monovalent Omicron XBB.1.5 mRNA RBD analogue vaccine, MAFB-7256a (DS- 5670d), was newly developed and approved in Japan in the Spring of 2024 for the prevention of COVID-19. However, clinical efficacy data for this vaccine are currently lacking. We previously established the Quantification of Antigen-specific Antibody Sequence (QASAS) method to assess the response to SARSCoV- 2 vaccination at the mRNA level using B-cell receptor (BCR) repertoire assays and the Coronavirus Antibody Database (CoV-AbDab). Here, we used this method to evaluate the immunogenicity of MAFB-7256a. We analyzed repeated blood samples using the QASAS method from three healthy volunteers before and after MAFB-7256a vaccination. BCR response increased rapidly one week post-vaccination and then decreased, as with conventional vaccine. Notably, the matched sequences after MAFB-7256a vaccination specifically bound to the receptor-binding domain (RBD), with no sequences binding to other epitopes. These results validate that MAFB-7256a is an effective vaccine that exclusively induces antibodies specific for the RBD, demonstrating its targeted immunogenic effect. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years. We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region. Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71–85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52–92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48–85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70–83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type. Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023–24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved. The Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

Introduction: To comprehensively identify and provide an overview of in vivo or clinical studies of nucleic acids (NA)-based vaccines against TB we included human or animal studies of NA vaccines for the prevention or treatment of TB and excluded in vitro or in silico research, studies of microorganisms other than M. tuberculosis, reviews, letters, and low-yield reports. Methods: We searched PubMed, Scopus, Embase, selected Web of Science and ProQuest databases, Google Scholar, eLIBRARY.RU, PROSPERO, OSF Registries, Cochrane CENTRAL, EU Clinical Trials Register, clinicaltrials.gov, and others through WHO International Clinical Trials Registry Platform Search Portal, AVMA and CABI databases, bioRxiv, medRxiv, and others through OSF Preprint Archive Search. We searched the same sources and Google for vaccine names (GX-70) and scanned reviews for references. Data on antigenic composition, delivery systems, adjuvants, and vaccine efficacy were charted and summarized descriptively. Results: A total of 18,157 records were identified, of which 968 were assessed for eligibility. No clinical studies were identified. 365 reports of 345 animal studies were included in the review. 342 (99.1%) studies involved DNA vaccines, and the remaining three focused on mRNA vaccines. 285 (82.6%) studies used single-antigen vaccines, while 48 (13.9%) used multiple antigens or combinations with adjuvants. Only 12 (3.5%) studies involved multiepitope vaccines. The most frequently used antigens were immunodominant secretory antigens (Ag85A, Ag85B, ESAT6), heat shock proteins, and cell wall proteins. Most studies delivered naked plasmid DNA intramuscularly without additional adjuvants. Only 4 of 17 studies comparing NA vaccines to BCG after M. tuberculosis challenge demonstrated superior protection in terms of bacterial load reduction. Some vaccine variants showed better efficacy compared to BCG. [ABSTRACT FROM AUTHOR]

Development of new vaccines tailored for difficult-to-target diseases is hampered by a lack of diverse adjuvants for human use, and none of the currently available adjuvants induce Th17 cells. Here, we develop a liposomal adjuvant, CAF®10b, that incorporates Mincle and Toll-like receptor 9 agonists. In parallel mouse and non-human primate studies comparing to CAF® adjuvants already in clinical trials, we report species-specific effects of adjuvant composition on the quality and magnitude of the responses. When combined with antigen, CAF®10b induces Th1 and Th17 responses and protection against a pulmonary infection with Mycobacterium tuberculosis in mice. In non-human primates, CAF®10b induces higher Th1 responses and robust Th17 responses detectable after six months, and systemic and pulmonary Th1 and Th17 recall responses, in a sterile model of local recall. Overall, CAF®10b drives robust memory antibody, Th1 and Th17 vaccine-responses via a non-mucosal immunization route across both rodent and primate species. There is a requirement for improved adjuvants to improve responses to vaccines, including adjuvants that induce Th17 cells. Here, the authors use a MINCLE and TLR9 agonist-based vaccine adjuvant and show induction of Th17 and mucosal immune responses to vaccine recall antigens in mice and non-human primate models of vaccination. [ABSTRACT FROM AUTHOR]

The emergence of vaccinomics and system vaccinology represents a transformative shift in immunization strategies, advocating for personalized vaccines tailored to individual genetic and immunological profiles. Integrating insights from genomics, transcriptomics, proteomics, and immunology, personalized vaccines offer the promise of enhanced efficacy and safety, revolutionizing the field of vaccinology. However, the development of personalized vaccines presents multifaceted challenges, including technical, ethical, economic, and regulatory considerations. Addressing these challenges is essential to ensure equitable access and safety of personalized vaccination strategies. Despite these hurdles, the potential of personalized vaccines to optimize responses and mitigate disease burden underscores the significance of ongoing research and collaboration in advancing precision medicine in immunization. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of tertiary lymphoid structures (TLSs) in cancer has been extensively studied, including predicting good prognosis and immunotherapy efficacy. Studies have shown that the induction strategy for the formation mechanism of TLSs is a new direction for tumor therapy, such as tumor vaccines against microorganisms. This article mainly describes the interaction between TLSs and microorganism-related cancer and provides new ideas for the clinical application of TLSs. Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues formed by the accumulation of lymphocytes and other components outside lymphoid organs. They have been shown to be widespread in cancers and have predictive effects on prognosis and immunotherapy efficacy; however, there is no standardized measurement guide. This paper provides a reference for future research. Moreover, the induction strategy for the formation mechanism of TLSs is a new direction for future cancer treatment, such as cancer vaccines for microorganisms. The effects of microorganisms on cancer are dual. The role of microorganisms, including bacteria, parasites, viruses, and fungi, in promoting cancer has been widely confirmed. However, the specific mechanism of their tumor suppressor effect, particularly the promotion of TLS formation, is currently unknown. In this review, we summarize the role of TLSs in cancer related to microbial infection and provide new ideas for further understanding their mechanisms of action in cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: The bacterial pathogen Chlamydia abortus is an important infectious cause of lamb death worldwide, causing abortion in the last few weeks of pregnancy. Existing live vaccines to protect sheep from abortion are effective but have been shown to cause infection and disease in some animals. We have recently developed a new, safer prototype subcellular vaccine comprising inactivated components of the pathogen that prevent abortions occurring in sheep and cannot itself cause disease. Initial testing of this new vaccine involved administration in two shots. In this latest investigation, we have reduced this to one single vaccination that contains less antigen without affecting its effectiveness. This low-antigen single-shot delivery reduces the costs associated with manufacturing the vaccine, increasing its viability as a new commercial product. Chlamydia abortus causes the disease ovine enzootic abortion, which is one of the most infectious causes of foetal death in small ruminants worldwide. While the disease can be controlled using live and inactivated commercial vaccines, there is scope for improvements in safety for both sheep and human handlers of the vaccines. We have previously reported the development of a new prototype vaccine based on a detergent-extracted outer membrane protein preparation of C. abortus that was determined to be more efficacious and safer than the commercial vaccines when administered in two inoculations three weeks apart. In this new study, we have developed this vaccine further by comparing its efficacy when delivered in one or two (1 × 20 µg and 2 × 10 µg) doses, as well as also comparing the effect of reducing the antigen content of the vaccine by 50% (2 × 5 µg and 1 × 10 µg). All vaccine formulations performed well in comparison to the unvaccinated challenge control group, with no significant differences observed between vaccine groups, demonstrating that the vaccine can be administered as a single inoculation and at a lower dose without compromising efficacy. Future studies should focus on further defining the optimal antigen dose to increase the commercial viability of the vaccine. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) patients face different health challenges when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population, due to both their immunocompromised state and the immunosuppressive therapies they receive. This systematic literature review, which follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) paradigm, explores the interactions between RA and SARS-CoV-2 infection, focusing on immunologic issues, disease management, vaccination, and adverse outcomes. In order to obtain the most relevant information, we systematically reviewed the specific literature from 1 January 2021 to 31 December 2023, based on the PRISMA method, by which we eventually selected 35 eligible articles, to which we added other ISI-indexed studies to enrich our results further. Consequently, we performed a funnel analysis to evaluate the potential for publication bias. Firstly, the data collected revealed the impact of the pandemic on RA diagnoses and the fear of face-to-face medical consultations that delayed adequate treatment. Secondly, cardiovascular and metabolic comorbidities increase the risk of prolonged COVID-19 symptoms, hospitalization, and severe COVID-19 outcomes for RA patients. With respect to immunosuppressive treatment used to control RA, it was observed that glucocorticoids (especially high-dose usage) and Rituximab (RTX) predispose the patients to poor SARS-CoV-2 outcomes, as opposed to Baricitinib and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) inhibitors. COVID-19 vaccination has proven effective and generally safe for RA patients in some studies, although therapies with Methotrexate (MTX), Abatacept (ABA), and RTX have been associated with impaired vaccine immune response. This systematic literature review brings updated and thorough information with respect to the immunological, clinical, and management of a complex immune-mediated inflammatory disease (IMID) like RA in the setting of COVID-19 and underlines the challenges faced by this group of patients. The lessons learned can be extended beyond the pandemic in shaping a more informed and compassionate healthcare system and offering long-term medical care for patients with RA. [ABSTRACT FROM AUTHOR]