Aug 2026· Expert Review of Vaccines· Vol 25 1, pp.
2722426
· 0 citations· 41 references
Medicine
TL;DR
Inactivated EV-A71 vaccines robust immunogenicity, high clinical efficacy, and an acceptable safety profile in children are compared.
Abstract
INTRODUCTION
Enterovirus 71 (EV-A71) is a principal cause of hand, foot, and mouth disease (HFMD), potentially leading to severe neurological complications in children. Inactivated EV-A71 vaccines have been introduced. This study compares the immunogenicity, safety, and efficacy of EV-A71 vaccines versus placebo in pediatric populations.
RESEARCH
Design
AND
Methods
Following a PROSPERO-registered protocol, RCTs involving EV-A71 in children were identified via PubMed, Scopus, Cochrane, and ClinicalTrials.gov. Two independent reviewers performed screening, extraction, and RoB assessments (RoB 2.0).
Results
Five phase III RCTs involving 36,659 children were included. EV-A71 vaccination significantly increased seropositivity across follow-up periods, including early (RR 5.8), medium-term (RR 3.09), and long-term (RR 2.95) response. Seroconversion was significantly higher in the vaccinated group (pooled RR 13.04, 95% CI 2.80-60.61; p < 0.001). Geometric mean titers, analyzed using the ratio of means approach, were significantly higher in the vaccinated group during early and medium-term follow-up. Vaccine efficacy against EV-A71-associated HFMD exceeded 98% (pooled RR 0.02, 95% CI 0.01-0.09; p = 0.0028; I2 = 50%). Solicited local and systemic adverse events were mild and comparable between groups.
Conclusion
Inactivated EV-A71 vaccines robust immunogenicity, high clinical efficacy, and an acceptable safety profile in children. Future studies should explore long-term protection, booster schedules, and multivalent formulations against non-EV-A71 serotypes.
4CMenB vaccine is authorized for protection against serogroup B invasive meningococcal disease (IMD). This study synthesized real-world evidence (RWE) data on effectiveness and impact of 4CMenB vaccine. A systematic search identified RWE on vaccine effectiveness (VE) and vaccine impact of 4CMenB in infants, children and adolescents. A meta-analysis was conducted of 4CMenB VE against serogroup B-IMD in infants and children. The primary meta-analysis used a random-effects model on data from five studies from five countries reporting VE in fully vaccinated infants and children, and estimated pooled VE at 79.7% (95% confidence interval 70.4, 86.1). In sensitivity analyzes, inclusion/exclusion of studies from the primary analysis did not materially change the results. Age-specific data in adolescents were summarized qualitatively. Data identified from Australia reported high effectiveness and impact in adolescents. This meta-analysis provides evidence of high 4CMenB VE against serogroup B-IMD in fully vaccinated infants and children across different geographic regions. Clinical trial registration: N/A.
Pavo Marijic, Katarzyna Jamróz-Dolińska, W. Margas et al.· npj Vaccines· 0 citations
Background Clostridioides difficile infection (CDI) significantly contributes to healthcare‐associated morbidity and mortality. Vaccination against C. difficile toxins may provide an effective preventive strategy, yet current data remain inconclusive. This meta‐analysis evaluates the efficacy, immunogenicity, and safety of the C. difficile toxoid vaccine. Methods We systematically searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from inception through August 2024. Eligible studies were randomized controlled trials enrolling adults aged 50–85 years that compared genetically detoxified Clostridioides difficile toxoid vaccines (50–200 µg) with placebo and reported clinical efficacy, immunogenicity, or safety outcomes. Random‐effects meta‐analyses were performed, with risk of bias assessed using RoB 2.0 and certainty of evidence graded using GRADE. The study was prospectively registered in PROSPERO (CRD42024597465). No external funding was received for this study. Results Eight trials (11,717 participants) showed no significant vaccine effect on overall CDI incidence (RR = 0.86; 95% CI 0.56–1.32; I2 = 0%) or severe CDI (RR = 0.25; 95% CI 0.02–3.75; I2 = 71%), though severe CDI risk trended lower in vaccinated groups. Immunogenicity analyses demonstrated significant seroconversion rates for toxin A (RR = 23.28; 95% CI 7.62–71.16; I2 = 0%) and toxin B (RR = 19.23; 95% CI 4.84–76.38; I2 = 0%). Vaccine recipients exhibited significantly elevated geometric mean concentrations (GMCs) for antitoxin A and B antibodies across various dosing regimens, particularly at higher doses (200 µg). Local adverse events, including pain (RR = 3.02; 95% CI 2.47–3.70), swelling (RR = 8.53; 95% CI 3.15–23.14), and erythema (RR = 6.78; 95% CI 2.35–19.61), were significantly increased postvaccination, but serious systemic reactions, infections, gastrointestinal disturbances, and mortality rates showed no significant differences compared to placebo. Interpretation of vaccine efficacy is limited by imprecision of effect estimates, heterogeneity in immunogenicity reporting, and the small number of trials evaluating severe CDI outcomes. Conclusion Clostridioides difficile toxoid vaccines induce strong humoral immune responses and demonstrate an acceptable safety profile but do not significantly reduce the overall CDI incidence. Evidence suggests a potential role in mitigating severe disease; however, clinical benefit remains uncertain due to imprecision and heterogeneity.
M. Shahzil, Z. Jamil, Saleha Azeem et al.· The Canadian journal of infe...· 0 citations
BACKGROUND
Shigella is the leading cause of morbidity and mortality in children younger than 5 years in low- and middle-income countries and is a major actor in antimicrobial resistance. An effective vaccine is urgently needed. SF2a-TT15, a conjugate featuring a synthetic 15-mer oligosaccharide surrogate of the O-antigen component of Shigella flexneri 2a (SF2a) lipopolysaccharide, was previously shown to be safe and immunogenic in a first-in-human study. We aimed to assess its safety and immunogenicity in infants from an endemic setting, the target population for a Shigella vaccine.
METHODS
We conducted a phase 2a, age-descending, dose-escalating, double-blind, randomised, placebo-controlled study at the Clinical Research Center, Kenya Medical Research Institute/Walter Reed Army Institute of Research (Kericho, Kenya). Healthy adults aged 18-50 years and healthy children aged 2-5 years with a weight-for-age Z score of -2 or more were randomly assigned (3:1) to receive a 10 μg oligosaccharide dose of SF2a-TT15 adjuvanted with aluminium hydroxide (alum) or matching placebo. Healthy infants aged 9 months plus or minus 1 month with a weight-for-age Z score of -2 or more were randomly assigned (3:3:3:3:1:1) in a stepwise manner to receive a 2 μg oligosaccharide dose of non-alum-adjuvanted SF2a-TT15, a 2 μg oligosaccharide dose of alum-adjuvanted SF2a-TT15, a 10 μg oligosaccharide dose of non-alum-adjuvanted SF2a-TT15, a 10 μg oligosaccharide dose of alum-adjuvanted SF2a-TT15, non-alum-adjuvanted placebo, or alum-adjuvanted placebo, concomitantly with routine measles-rubella vaccination. Study products were administered intramuscularly on day 0, 90, and 270, with a 6-month follow-up after the last injection. The randomisation sequence was computer-generated and randomisation was stratified by cohort and treatment group. Syringes were over-labelled before injection to maintain masking; all clinical site teams were masked except the pharmacist team, including the pharmacy data quality monitoring team, and one person in the Institut Pasteur team. All participants were also masked. Progression between cohorts and dose levels was overseen by an independent data monitoring committee. The primary outcomes were the incidence of adverse events in all cohorts and immunogenicity in the infant cohort, as measured at days 14 and 28 after each injection and at the end of the study by serum IgG antibodies to SF2a lipopolysaccharide and proportion of responders. Safety endpoints were analysed in all participants receiving at least one injection and immunogenicity endpoints were analysed in the full analysis set and in the per-protocol analysis set. This study is registered with ClinicalTrials.gov, NCT04602975, and is completed.
FINDINGS
Enrolment was between Oct 26, 2020, and Jan 5, 2022. 54 adults were screened for eligibility, 16 of whom were enrolled and randomly assigned to the adjuvanted 10 μg oligosaccharide dose (n=12) or adjuvanted placebo (n=4). 30 children were screened for eligibility, 16 of whom were enrolled and randomly assigned to the adjuvanted 10 μg oligosaccharide dose (n=12) or adjuvanted placebo (n=4). 413 infants were screened for eligibility, 216 of whom were enrolled and randomly assigned to the non-adjuvanted 2 μg oligosaccharide dose (n=46), the adjuvanted 2 μg oligosaccharide dose (n=44), the non-adjuvanted 10 μg oligosaccharide dose (n=41), the adjuvanted 10 μg oligosaccharide dose (n=43), non-adjuvanted placebo (n=22), or adjuvanted placebo (n=20). 112 (52%) of 215 infants in the safety analysis set were female and 103 (48%) were male. The SF2a-TT15 glycoconjugate was well tolerated and induced high serum IgG geometric mean titres (GMTs) to SF2a lipopolysaccharide in adults and children. In infants, SF2a-TT15 was well tolerated at both doses, adjuvanted or non-adjuvanted, with no vaccine-related serious adverse events. 202 (94%) of 216 infants had at least one unsolicited adverse event. 182 (90%) of these infants had adverse events considered not related to study products. No significant differences in the frequency of unsolicited adverse events were reported between any treatment groups (p>0·05 for all comparisons). 1235 adverse events were recorded in the infant cohort, most being unrelated to the study product (1226 [99%]) and of mild (744 [60%]) or moderate (435 [35%]) grading. At 28 days after each injection and for both doses, adjuvanted or non-adjuvanted, SF2a-TT15 induced significantly higher serum IgG GMTs to SF2a lipopolysaccharide compared with corresponding GMTs in placebo recipients (p=0·047 for the non-adjuvanted 2 μg oligosaccharide dose 28 days after the first injection and p<0·001 for all the other comparisons). The highest GMTs were elicited in the adjuvanted 10 μg oligosaccharide dose group (11 240·0 [95% CI 6187·6-20 418·0]), corresponding to a geometric mean ratio (GMR) of 55·0 (95% CI 30·3-99·7) with 93·8% (95% CI 79·2-99·2) of responders at 14 days after the first injection, and increased to 28 528·3 (18 805·1-43 279·0), corresponding to a GMR of 139·6 (79·5-245·2) with 100% (89·1-100·0) of responders at 14 days after the second injection, with no further increase after the boost vaccine. The adjuvanted 2 μg oligosaccharide dose group had significantly higher serum IgG GMTs to SF2a lipopolysaccharide than the non-adjuvanted 2 μg oligosaccharide dose group (p<0·001 at day 28 after the two first injections, p=0·022 at 28 days after the boost vaccine), but GMT were not significantly different between the adjuvanted and non-adjuvanted 10 μg oligosaccharide dose SF2a-TT15 groups (p>0·5 for all timepoints). At the end of the study, for both doses, adjuvanted or not, GMTs were decreased but were still significantly elevated compared with the placebo group (p<0·001).
INTERPRETATION
SF2a-TT15 is well tolerated and strongly immunogenic in Kenyan infants, showing potential for further development. Available data support advancing a multivalent synthetic glycan-based Shigella vaccine.
FUNDING
Gates Foundation, The Wellcome Trust, The European Union Seventh Framework Programme, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases, and Institut Pasteur.
TRANSLATION
For the Kiswahili translation of the abstract see Supplementary Materials section.
F. Sawe, Lucy Koech, Souhir Neffati et al.· Lancet. Infectious Diseases...· 0 citations
RATIONALE
Follow-up of pre-licensure trial participants potentially informs a vaccine's long-term safety profile.
DESIGN
This prospective study enrolled participants from the first clinical trials of ChAdOx1 nCoV-19 vaccine, many of whom subsequently received COVID-19 vaccines in the UK vaccination programme. Serious adverse events (SAEs) and adverse events of special interest (AESIs) were captured. AESI selection was based on Brighton Collaboration definitions.
RESULTS
Between September 2021 and April 2022, 4470 participants enrolled (58% female, median age 50 years); 3845/4470 (86.0%) completed the study. Median follow-up was 11.77 months; total follow-up was 48,116 person-months. There were 174 SAEs and 71 AESIs (33 events recorded as both) in 195 participants, including 5 deaths. Immunology data were available for a small subset of participants; total IgG against trimeric SARS-CoV-2 spike protein tended to increase during the study.
CONCLUSIONS
Although no emergent safety signals were detected, continued post-marketing surveillance remains imperative, particularly for neurological disorders.
EUDRACT NUMBER
2021-003382-36.
Narges Ebrahimi, Philip de Whalley, Nasir Kanji et al.· Vaccine· 0 citations
BACKGROUND
COVID-19 vaccines have significantly reduced mortality and are safe for healthy children; however, research in pediatric populations with juvenile immune-mediated inflammatory diseases (IMIDs) is limited.
METHODS
The Brazilian multicenter longitudinal SAFER-Study evaluates immunogenicity and safety of the BNT162b2/Pfizer vaccine in IMID patients. The juvenile cohort enrolled patients aged 12-17 years between August and December 2021 and compared them with adults under 40 years from the adult cohort. Safety was assessed by monitoring post-vaccination adverse events (AEs), immunogenicity was measured by IgG antibodies against the SARS-CoV-2 spike receptor-binding domain and seroconversion rates.
RESULTS
A total of 123 participants were included: 86 adolescents and 37 adult controls. In adolescents, local AEs were most frequent; no serious or life-threatening AEs occurred. Significant increases in IgG-S levels were observed after the two doses in both cohorts (p < 0.001). Seroconversion after the second dose reached 97% overall and 100% after the third dose. In juvenile SLE and JIA patients, vaccination did not significantly affect disease activity.
CONCLUSION
The BNT162b2 vaccine was safe and immunogenic in adolescents with IMIDs, including those with high immunosuppression and comorbidities, showing similar responses to adults. These findings support vaccination in this vulnerable population and contribute to evidence-based recommendations.
IMPACT
BNT162b2 COVID-19 vaccine demonstrated a favorable safety profile and immunogenicity in adolescents with juvenile immune-mediated inflammatory diseases (IMID), with responses comparable to those observed in adults. Real life data on this population remain limited, and further evidence regarding vaccine safety and immunogenicity is needed. This study represents the first multicenter, longitudinal registry of Brazilian adolescents with IMID receiving BNT162b2. Comprehensive data on the safety and immunogenicity of BNT162b2 in highly immunosuppressed adolescents with IMID and comorbidities are crucial to guide clinical decision-making, mitigate vaccine hesitancy, and enhance vaccination coverage within this vulnerable population.
C. Gadelha, Maria Teresa Terreri, Ana Paula N Burian et al.· Pediatric Research· 0 citations
BACKGROUND
Mpox is a zoonotic disease caused by the monkeypox virus (MPXV) that became a global health concern following the 2022 outbreak. It poses a significant threat to immunocompromised individuals, children, and pregnant persons. Disease spread in the Democratic Republic of the Congo (DRC) and propagation to other countries has led to recent declarations of public health emergencies. Smallpox vaccination cessation has further heightened population vulnerability to MPXV. In response, MVA-BN and LC16m8, vaccinia-based vaccines originally developed for smallpox, have been repurposed for mpox, demonstrating promising safety and immunogenicity profiles. Despite these advancements, challenges remain in vaccine distribution and in understanding vaccine efficacy across populations, particularly in key at-risk groups. Available evidence remains fragmented and largely derived from adult populations, with limited data in pregnant persons, children, and adolescents. This living systematic review (LSR) aims to evaluate the safety, efficacy, effectiveness, and immunogenicity of mpox vaccines across populations, with particular focus on pregnant persons, children, and adolescents.
METHODS
We aim to conduct a LSR and meta-analysis based on biweekly searches of medical databases and clinical trial registries from inception to the current date to systematically identify relevant studies of mpox vaccines across populations. Pairs of reviewers will independently select eligible studies, extract data, and assess the risk of bias. We will include randomized clinical trials, quasi-experimental studies, cohort studies, case-control studies, cross-sectional studies, and case reports. Primary outcomes will include safety, efficacy/effectiveness, and immunogenicity of mpox vaccines across populations, including outcomes in pregnant persons (with neonatal outcomes), children, and adolescents. Meta-analyses will be conducted, including prespecified subgroup and sensitivity analyses. We will use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence.
DISCUSSION
This LSR will synthesize evidence on mpox vaccines across populations, with particular focus on pregnant persons, children, and adolescents. As mpox continues to pose a global threat, particularly in endemic and low-resource settings, timely and rigorous assessment of vaccine performance is essential to guide equitable immunization policies and maternal-child health strategies.
SYSTEMATIC REVIEW REGISTRATION
International Prospective Register of Systematic Reviews (PROSPERO): CRD42024554330 (pregnant persons) and CRD42024556977 (children and adolescents).
J. Ballivian, Agustín Ciapponi, M. Berrueta et al.· Systematic Reviews· 0 citations
