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Background: A primary goal of this study was to establish the serological mechanistic correlate of protection (mCoP) for an inactivated Enterovirus 71 (EV71) vaccine. Methods: We used the Prentice criterion framework and scaled logit model to explore the relationship between the neutralizing antibody (NTAb) and EV71-associated disease, and to build a protection curve for estimating the efficacy of EV71 vaccine. Data of NTAb at day 56 post-vaccination and the occurrence of EV71-associated disease during a 12-month follow-up period were collected from a phase 3 efficacy trial of EV71 vaccine in this study.Results: NTAb at day 56 post-vaccination in participants met the Prentice criterion framework. According to the protection curve, the antibody levels of 14.7, 27.8, 55.7, 129.0 and 459.4 (U/mL) were associated with 50%, 60%, 70%, 80% and 90% clinical protection rate, respectively. Vaccine efficacy predicted by the model was 81.5%, which was very similar to the actual vaccine efficacy of 80.4% (95% CI, 58.2, 90.8) observed in the phase 3 trial. Conclusions: NTAb titers post-vaccination can be validated as mCoP for evaluating the efficacy of an inactivated enterovirus 71 vaccine, with a titers of 14.7 (U/ml) as a surrogate associated with the protection of 50% against EV71-associated disease.

Objectives: This study aimed to evaluate the immunogenicity and safety of a hepatitis E (HE) vaccine using an accelerated vaccination schedule (vaccine doses at 0, 7 and 21 days). Methods: A total of 126 participants aged 18 years were randomly assigned to receive the hepatitis E virus vaccine in either the accelerated group (0, 7 and 21 days) or the routine group (0, 1 and 6 months). Serology samples were obtained at 0, 21, 28 and 51 days, and 7 months in the accelerated group, or 0, 1, 2 and 7 months in the routine group after the first vaccine injection. Adverse events (AEs) reported during the whole study were analysed. Results: A total of 126 participants were randomized, 63 for each group. Sixty-two participants in the accelerated group and 63 in the routine group received at least one dose of vaccine; 57 and 63 participants received all three doses and were included in per-protocol set, respectively. In the per-protocol population, at 1 month after the last dose (accelerated group at 51 days versus routine group at 7 months), the seropositive rates were both 100% (57/57 and 63/63, respectively), and the geometric mean concentrations (GMCs) were 8.51 WHO units/mL (95% CI 6.73e10.76) in the accelerated group and 9.67 WHO units/mL (95% CI 7.67e12.20) in the routine group. The ratio of the accelerated group GMC to the routine group GMC was 0.88 (95% CI 0.61e2.17, lower limit of 95% CI > 0.5), indicating that the accelerated vaccination schedule was non-inferior to the routine one. The overall incidence rates of solicited AEs in the accelerated and routine groups were 32.26% (20/62) and 30.16% (19/63), respectively (p 0.800). Most AEs were moderate. Conclusions: An accelerated schedule is safe and provides protective antibodies in a shorter time compared with the routine schedule. The accelerated schedule should be recommended to adults who are travelling on short notice to an HE-endemic area or during an HE outbreak (Clinical Trial Registration.

Background: Short-term dynamic changes in neutralizing antibodies against EV71 and EV71-IgM after inactivated EV71 vaccine injection are unknown. Methods: This study was designed as a randomized, open-label study and was registered at ClinicalTrials.gov (NCT03278132). In total, 120 healthy infants aged 6-35 months were randomized 1:1:1 to provide a second blood sample on day 10, day 20, or day 30 after the first vaccine dose, respectively. Results: According to the per-protocol set, a rapid immune response against EV71 was observed 10 days after the first EV71 vaccine dose, with antibody titers ≥1:8 in 89.19% of participants (95% CI: 74.58-96.97%) on day 10, in 80.65% (95% CI: 62.53-92.55%) on day 20, in 66.67% (95% CI: 49.03-81.44%) on day 30, and in 100% (95% CI: 96.52%-.) on day 60. Based on an ELISA, the percentages of participants positive for EV71-IgM on day 0 and day 60 were 1.71% (2 out of 117) and 82.86% (87 out of 105), respectively. Conclusions: The EV71 vaccine could be used for contingency vaccination to further control EV71associated disease outbreaks. Caution should be taken in using the EV71-IgM test for rapid EV71 infection diagnosis after EV71 vaccine administration. Clinical Trial Registration: ClinicalTrials.gov NCT03278132 ARTICLE HISTORY

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