Safety and Efficacy of a Third Dose of BNT162b2 Covid-19 Vaccine.

BACKGROUND: Active immunization with the BNT162b2 vaccine (Pfizer-BioNTech) has been a critical mitigation tool against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the coronavirus disease 2019 (Covid-19) pandemic. In light of reports of waning protection occurring 6 months after the primary two-dose vaccine series, data are needed on the safety and efficacy of offering a third (booster) dose in persons 16 years of age or older. METHODS: In this ongoing, placebo-controlled, randomized, phase 3 trial, we assigned participants who had received two 30-µg doses of the BNT162b2 vaccine at least 6 months earlier to be injected with a third dose of the BNT162b2 vaccine or with placebo. We assessed vaccine safety and efficacy against Covid-19 starting 7 days after the third dose. RESULTS: A total of 5081 participants received a third BNT162b2 dose and 5044 received placebo. The median interval between dose 2 and dose 3 was 10.8 months in the vaccine group and 10.7 months in the placebo group; the median follow-up was 2.5 months. Local and systemic reactogenicity events from the third dose were generally of low grade. No new safety signals were identified, and no cases of myocarditis or pericarditis were reported. Among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated, Covid-19 with onset at least 7 days after dose 3 was observed in 6 participants in the vaccine group and in 123 participants in the placebo group, which corresponded to a relative vaccine efficacy of 95.3% (95% confidence interval, 89.5 to 98.3). CONCLUSIONS: A third dose of the BNT162b2 vaccine administered a median of 10.8 months after the second dose provided 95.3% efficacy against Covid-19 as compared with two doses of the BNT162b2 vaccine during a median follow-up of 2.5 months. (Funded by BioNTech and Pfizer; C4591031 ClinicalTrials.gov number, NCT04955626.).

Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents.

BACKGROUND: Until very recently, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had not been authorized for emergency use in persons younger than 16 years of age. Safe, effective vaccines are needed to protect this population, facilitate in-person learning and socialization, and contribute to herd immunity. METHODS: In this ongoing multinational, placebo-controlled, observer-blinded trial, we randomly assigned participants in a 1:1 ratio to receive two injections, 21 days apart, of 30 µg of BNT162b2 or placebo. Noninferiority of the immune response to BNT162b2 in 12-to-15-year-old participants as compared with that in 16-to-25-year-old participants was an immunogenicity objective. Safety (reactogenicity and adverse events) and efficacy against confirmed coronavirus disease 2019 (Covid-19; onset, ≥7 days after dose 2) in the 12-to-15-year-old cohort were assessed. RESULTS: Overall, 2260 adolescents 12 to 15 years of age received injections; 1131 received BNT162b2, and 1129 received placebo. As has been found in other age groups, BNT162b2 had a favorable safety and side-effect profile, with mainly transient mild-to-moderate reactogenicity (predominantly injection-site pain [in 79 to 86% of participants], fatigue [in 60 to 66%], and headache [in 55 to 65%]); there were no vaccine-related serious adverse events and few overall severe adverse events. The geometric mean ratio of SARS-CoV-2 50% neutralizing titers after dose 2 in 12-to-15-year-old participants relative to 16-to-25-year-old participants was 1.76 (95% confidence interval [CI], 1.47 to 2.10), which met the noninferiority criterion of a lower boundary of the two-sided 95% confidence interval greater than 0.67 and indicated a greater response in the 12-to-15-year-old cohort. Among participants without evidence of previous SARS-CoV-2 infection, no Covid-19 cases with an onset of 7 or more days after dose 2 were noted among BNT162b2 recipients, and 16 cases occurred among placebo recipients. The observed vaccine efficacy was 100% (95% CI, 75.3 to 100). CONCLUSIONS: The BNT162b2 vaccine in 12-to-15-year-old recipients had a favorable safety profile, produced a greater immune response than in young adults, and was highly effective against Covid-19. (Funded by BioNTech and Pfizer; C4591001 ClinicalTrials.gov number, NCT04368728.).

Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine in Healthy Meningococcal-Naïve Children 2-9 Years of Age: A Phase III, Randomized Study.

BACKGROUND: Invasive meningococcal disease is a major cause of meningitis in children. An investigational meningococcal (serogroups A, C, Y, and W) tetanus toxoid conjugate vaccine (MenACYW-TT) could offer protection against invasive meningococcal disease in this population. This phase III study assessed the immunogenicity and safety of MenACYW-TT in children compared with a licensed quadrivalent meningococcal vaccine conjugated with diphtheria protein CRM197 (MenACWY-CRM). METHODS: Healthy children 2-9 years of age in the United States, including Puerto Rico, were randomized (1:1) to receive MenACYW-TT (n = 499) or MenACWY-CRM (n = 501) (NCT03077438). Meningococcal antibody titers to the 4 vaccine serogroups were measured using a serum bactericidal antibody assay with human complement (hSBA) before and at day 30 after vaccination. Noninferiority between the vaccine groups was assessed by comparing seroresponse rates (postvaccination titers ≥1:16 when prevaccination titers were <1:8, or ≥4-fold increase if prevaccination titers were ≥1:8) to the 4 serogroups at day 30. Safety was monitored. RESULTS: The proportion of participants achieving seroresponse at day 30 in the MenACYW-TT group was noninferior to the MenACWY-CRM group (A: 55.4% vs. 47.8%; C: 95.2% vs. 47.8%; W: 78.8% vs. 64.1%; Y: 91.5% vs. 79.3%, respectively). Geometric mean titers for serogroups C, W, and Y were higher with MenACYW-TT than for MenACWY-CRM. Both vaccines were well-tolerated and had similar safety profiles. CONCLUSIONS: MenACYW-TT was well-tolerated in children and achieved noninferior immune responses to MenACWY-CRM against each of the 4 vaccine serogroups.

Antibody persistence and safety and immunogenicity of a second booster dose nine years after a first booster vaccination with a reduced antigen diphtheria-tetanus-acellular pertussis vaccine (Tdap) in adults.

BACKGROUND: Over the last decades, pertussis showed periodic increases in its incidence among adults, despite being a vaccine-preventable disease. METHODS: This phase III, multicenter, extension study (NCT00489970) was conducted in adults from the United States, followed at Year (Y) 5 and Y9 post-vaccination with a dose of reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine containing either 3 (Tdap-B group) or 5 pertussis components (Tdap-A group). Willing participants in Tdap groups and newly-recruited participants (Control group) received one Tdap-B dose at Y9. Antibody persistence (at Y5 and Y9) and safety of Tdap-B at Y9 were assessed. Non-inferiority of immune response elicited by 2 Tdap doses was evaluated at Y9: (i) versus one Tdap-B dose for diphtheria and tetanus in terms of seroprotection rates; (ii) for all antigens in terms of booster response rates (Tdap-B and Tdap-A groups versus Control group); and (iii) for pertussis antigens in terms of geometric mean concentrations (GMCs) versus a 3-dose series of a combined diphtheria-tetanus-acellular pertussis vaccine (DTPa) administered during infancy. RESULTS: 1257 participants were enrolled at Y5 and 809 participants were vaccinated at Y9. Seroprotection rates in both Tdap groups were ≥98.4% and ≥98.0% (Y5) and ≥98.3% and ≥98.1% (Y9) for diphtheria and tetanus, respectively. For pertussis antigens, antibody concentrations above assay cut-offs were observed for ≥76.6% (Y5) and ≥84.9% (Y9) of participants in Tdap groups. At Y9, one month post-Tdap vaccination, comparable seroprotection/seropositivity rates and antibody GMCs were observed among groups. Non-inferiority of immune responses in both Tdap groups was demonstrated when compared to the Control group for diphtheria and tetanus and to a 3-dose DTPa series for pertussis antigens. Non-inferiority criteria in terms of booster response were not met for all antigens. No safety concerns were raised. CONCLUSION: A second dose of Tdap-B administered in adults, 9 years after initial Tdap vaccination, is immunogenic and well-tolerated.

Non-inferiority of mammalian cell-derived quadrivalent subunit influenza virus vaccines compared to trivalent subunit influenza virus vaccines in healthy children: a phase III randomized, multicenter, double-blind clinical trial.

OBJECTIVES: The safety and immunogenicity of mammalian cell-derived quadrivalent influenza vaccine (QIVc) as compared with trivalent influenza vaccines (TIV1c/TIV2c) was evaluated in children aged ≥4 to <18 years. METHODS: Two thousand three hundred and thirty-three subjects were randomized 2:1:1 to receive either one or two doses of study vaccine depending on previous vaccination status. Hemagglutination inhibition antibody responses for all four influenza strains were performed 3 weeks after the last dose. Reactogenicity and safety were also assessed (ClinicalTrials.gov: NCT01992107). RESULTS: QIVc met the non-inferiority criteria against all four vaccine strains and demonstrated superiority for both influenza B strains over the unmatched B lineage included in the comparator vaccines, when geometric mean titers and seroconversion rates were compared at 3 weeks after the last vaccination. Similar percentages of subjects experienced solicited and unsolicited adverse events (AEs) across all subgroups. Unsolicited AEs, serious AEs, medically attended AEs, and new onset chronic disease were reported in comparable percentages of subjects in all study groups. No vaccine-related serious AEs or deaths occurred. CONCLUSIONS: QIVc demonstrated a similar safety profile and immunogenicity responses against all four vaccine strains without signs of immune interference on addition of an alternate lineage B strain compared with TIV1c/TIV2c and may provide broader protection against both influenza B lineages in children.