Background: The three commercial Enterovirus 71 (EV71) inactivated vaccines which have effectively controlled the EV71 pandemic currently rely on inherent variable in vivo potency methods for batch release. To align with 3R (Replacement, Reduction, Refinement) principles and enhance quality control, this study referred to WHO guidelines and the European Pharmacopoeia to develop in vitro relative potency (IVRP) methods. Methods: Working standards tracing to phase 3 clinical vaccines were established. Manufacture-specific IVRP methods were developed and validated per ICH Q14/Q2(R2), utilizing conformational epitope-targeting neutralizing monoclonal antibodies (MAbs). One of the MAbs (CT11F9) recognition sites was clarified with Cryo-EM. Subsequently, the performance of IVRP was assessed using varied concentrations and heat-treated vaccines. The correlation between IVRP and in vivo methods was analyzed, followed by setting IVRP specifications. Results: The manufacturer-specific working standard exhibited ED50 values comparable to those of related phase 3 clinical vaccines. All IVRP methods achieved a relative bias/precision/total error ≤ 15%. The IVRP methods correlated with in vivo methods (p < 0.05, r > 0.9) can discriminate EV71 antigen concentrations (p < 0.01, r > 0.99) and indicate the stability of the vaccines. Cryo-EM was adopted to identify the epitopes recognized by CT11F9, revealing that this neutralizing antibody recognizes a conformational epitope spanning VP1-3 of the same protomer. Using 31–47 batches of commercial vaccines, IVRP specifications were proposed as 0.56–1.35, 0.58–1.40, and 0.54–1.50. Conclusions: Based on conformational epitope-targeting neutralizing MAbs, manufacturer-specific IVRP methods, which were sensitive to process variations and correlated with in vivo results, have been established. IVRP methods provide a reliable, animal-free alternative for EV71 vaccine batch release.

Objectives: This randomized, double-blind, active-controlled non-inferiority phase 4 clinical trial was conducted to evaluate the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) compared to an active comparator vaccine. Methods: Pneumococcal vaccine-naïve participants aged ≥2 years were randomly assigned in a 2:1 ratio to receive a single dose of either the investigational vaccine (n = 1199) or the comparator vaccine (n = 600). Immunogenicity was evaluated at baseline and 30 days post-vaccination by measuring serotype-specific IgG antibodies against all 23 pneumococcal serotypes using enzyme-linked immunosorbent assay. The primary outcome was seroconversion, defined as a ≥two-fold increase in serotype-specific IgG antibody titers at day 30 compared to baseline. Results: At one month post-vaccination, seroconversion rates for each of the 23 serotypes ranged from 59.22% to 95.67% in the treatment group, compared to 59.66% to 94.07% in the control group. Non-inferiority was demonstrated for all serotypes, with the lower bounds of the 95% confidence intervals (95%CI) for rate differences exceeding the predefined −10% margin. Moreover, superiority was observed for 12 serotypes (6B, 23F, 1, 2, 4, 8, 9N, 9V, 11A, 15B, 17F and 18C), as the lower bounds of their 95%CI for rate differences were above 0. Adverse reactions were reported in 236 (19.68%) participants of the investigational group and 118 (19.67%) of the control group within 30 days post-vaccination, with no significant differences between groups. Conclusions: The PPSV23 vaccine administered among individual aged ≥2 years was safe, well tolerated and immunogenic, eliciting an immune response either comparable to or higher than control vaccine. These findings support its use as a safe and effective option for pneumococcal immunization.

Objectives: In this study, we aimed to evaluate the non-inferiority of a quadrivalent influenza vaccine (QIV) developed by Sinovac Biotech Co., Ltd. (Sinovac, Beijing, China) by comparing its immunogenicity and safety with a comparator QIV (Vaxigrip Tetra^®) in a population aged 3 years and older in Chile and the Philippines. Methods: A phase 3, non-inferiority, double-blind, randomized controlled, multicenter clinical trial was conducted in the southern hemisphere (SH) 2023 influenza season. Participants aged ≥ 3 years old with stable health were randomized 1:1 to receive either Sinovac QIV or comparator QIV. The co-primary outcomes were immunological non-inferiority for Sinovac QIV versus the comparator against each strain contained in the vaccines in terms of seroconversion rates (SCRs) and geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibodies 28 days after final vaccination. Results: A total of 2039 participants were vaccinated (1019 Sinovac QIV; 1020 comparator QIV). Sinovac QIV induced non-inferior immune responses to all four strains as compared to comparator QIV, with slightly higher GMTs than those of comparator QIV: GMT ratios (lower limit 95% confidence interval (CI)) were 1.8 (1.6) for A(H1N1), 1.4 (1.3) for A (H3N2), 1.3 (1.1) for B Victoria and 1.2 (1.1) for B Yamagata; observed seroconversion rate differences (lower limit 95% CI) were 9.6% (6.7) for A(H1N1), 7.0% (3.5) for A(H3N2), 2.4% (−0.03) for B Victoria and 6.8% (3.0) for B Yamagata. Adverse reactions were similar across the two groups and no vaccine-related serious adverse events were reported. Conclusions: The immunogenicity of Sinovac QIV was non-inferior to that of the comparator QIV in these populations aged 3 years and older, and safety was comparable.

Influenza is a major cause of morbidity and mortality. The protective effect of a trivalent influenza vaccine (TIV) is undetermined in military personnel. We conducted an open-label, cluster randomized trial on active-duty servicemen of Beijing, Tianjin, and Shijiazhuang, who were randomly assigned to receive either a single dose of TIV or no treatment, according to cluster randomized sampling. The subjects were then followed for a maximum of six months to assess the incidence of laboratory-confirmed influenza. A total of 5445 subjects in 114 clusters received one dose of TIV before the 2015/2016 influenza season. Laboratory-confirmed influenza was identified in 18 in the vaccine group compared with 87 in the control group (6031 subjects in 114 clusters), resulting in a vaccine effectiveness (VE) of 76.4% (95%CI: 60.7 to 85.8) against laboratory-confirmed influenza. Influenza-like illness was diagnosed in 132 in the vaccine group compared with 420 in the control group, resulting in a VE of 64.1% (95%CI: 56.2 to 70.6). The estimated VE against influenza B viruses was 80.5% (95%CI: 65.6 to 88.9) and 8.6% (95%CI: −241 to 75.5) against influenza A viruses. In conclusion, the trivalent influenza vaccine is moderately effective, highly immunogenic, and generally safe to use in healthy male military servicemen.