Safety and immunogenicity of a quadrivalent inactivated subunit non-adjuvanted influenza vaccine: A randomized, double-blind, active-controlled phase 1 clinical trial.

Abstract

Quadrivalent influenza inactivated vaccine (IIV4) is more likely to provide wider protection against yearly circulating influenza viruses than trivalent inactivated influenza vaccine (IIV3). In this study, a total of 320 participants were allocated to four age cohorts (6-35\xa0months, 3-8\xa0years, 9-17\xa0years, and\xa0≥\xa018\xa0years; 80 participants/cohort) according to their actual date of birth. Participants in each cohort were randomly assigned to two groups to receive intramuscular injection of the trial vaccine or the comparative vaccine in a one-dose (3-8\xa0years, 9-17\xa0years,and\xa0≥\xa018\xa0years) schedule on day 0 or two-dose (6-35\xa0months cohort) schedule on day 0 and 28. The first objective is to evaluate the safety and immunogenicity of the full-dose subunit non-adjuvanted IIV4 (FD-subunit NAIIV4) we developed versus an active-control, China-licensed split-virion NAIIV4, in people\xa0≥\xa03\xa0years. The second objective is to evaluate the safety and immunogenicity of FD-subunit NAIIV4 versus the half-dose (HD-subunit NAIIV4) in toddlers aged 6-35\xa0months. Results showed that all adverse reactions noted were rare, mild, and self-limited. In\xa0≥\xa03\xa0years cohorts, systemic adverse reactions in FD-subunit NAIIV4 groups were less than the active control split-virion NAIIV4 groups ([Systemic adverse reaction rates (95%CI)], 15.0 (8.6-21.4) versus 19.2(12.1-26.2), p\xa0=\xa00.391). The overall seroprotection efficacy after vaccination were comparable between FD-subunit NAIIV4 and the active control split-virion NAIIV4([Seroprotection rates (95%CI)], H1N1, 99.2(81.3-100.0) versus 94.9(90.9-98.9), p\xa0=\xa00.117; H3N2, 81.7(74.7-88.6) versus 82.1(75.1-89.0), p\xa0=\xa00.939; BV, 75.8(68.2-83.5) versus 74.4(66.4-82.3), p\xa0=\xa00.793; BY, 94.2(90.0-98.4) versus 92.3(87.5-97.1), p\xa0=\xa00.568). Additionally, FD-subunit NAIIV4 has comparable safety and better seroprotection versus that of the half-dose in 6-35\xa0months toddlers groups ([Total adverse reaction rates (95%CI)], 37.5(18.5-56.5) versus 47.5(26.1-68.9), p\xa0=\xa00.366) ([Seroprotection rates (95%CI)], H1N1, 85(56.4-100.0) versus 75.7(47.6-100.0), p\xa0=\xa00.117; H3N2, 50(28.1-71.9) versus 29.7(12.2-47.3), p\xa0=\xa00.070; BV, 75(48.2-100.0) versus 29.7(12.2-47.3), p\xa0<\xa00.001; BY, 75(48.2-100.0) versus 56.8(32.5-81.0), p\xa0=\xa00.091). As a result, the FD-subunit NAIIV4 we developed is safe and effective to provide broader and adequate protection against the circulating influenza viruses during 2018-2019, which could be an essential component of the global preventive strategy for influenza pandemic.