An egg culture-based quadrivalent inactivated nonadjuvanted subunit influenza vaccine was found to be safe and noninferior to the split-virion influenza vaccine, according to results of a randomized, double-blinded, active-controlled phase 3 trial, published in Vaccine.
Participants (N=3000) included in this study were enrolled between April 2020 and August 2021 at 2 sites in China. Researchers evaluated the safety and immunogenicity of an influenza subunit vs split-virion vaccine. Both vaccines were formulated using antigens from influenza vaccine strains recommended by the World Health Organization for the 2019 to 2020 influenza season, and both were egg culture-based quadrivalent inactivated nonadjuvanted vaccines. Participants were stratified into 4 groups by age, and those in each group were randomly assigned in a 1:1 fashion to receive either the subunit (n=1499) or split-virion (n=1498) influenza vaccine. Participants aged between 3 and 8 years received a 2-dose vaccine series, and the remaining participants received a single vaccine dose.
Among the 4 groups, participants in group 1 (n=799) were aged 3 to 8 years, those in group 2 (n=700) were 9 to 17 years, those in group 3 (n=700) were 18 to 64 years, and those in group 4 (n=800) were 65 years and older. Baseline characteristics among participants in each group were similar between those assigned to the subunit vaccine and those assigned to the split-virion vaccine.
No significant differences between the subunit and split-virion vaccines were noted in regard to safety profiles. Among all participants, adverse events (AEs) occurred among 227 (15.13%) and 216 (14.40%) of those who received the subunit and split-virion vaccines, respectively (P >.999). For all participants, the most common local AE was injection site pain, and the most common systemic AE was fever.
Among participants in group 1, the rate of fever following receipt of the second vaccine dose was significantly decreased among those who received the subunit vaccine vs those who received the split-virion vaccine (0.51% vs 2.53%; P =.021).
Preexisting immune responses, defined as hemagglutination inhibition (HAI) titers of 10 or more were observed at baseline among 80.73%, 91.93%, 36.57%, and 90.40% of all participants for the H1N1, H3N2, BV, and BY influenza virus strains, respectively. No significant differences in preexisting immunity responses were observed on the basis of age among participants in groups 1, 3, and 4. However, the number of participants with resistance to H1N1 at baseline vs postvaccination was increased among those in group 2 (62.45% vs 52.93%; P =.012).
Further analysis between the subunit vs split-virion vaccines showed that the subunit vaccine elicited stronger immune responses to the H1N1 (geometric mean titers [GMTs], 400.39 vs 333.46; P <.001), H3N2 (GMTs, 436.71 vs 384.13; P =.041), BV (GMTs, 77.80 vs 67.90; P =.001), and BY (GMTs, 267.60 vs 180.63; P <.001) strains. In addition, geometric mean fold increase (GMFI) values were increased among participants who received the subunit vaccine for all 4 influenza strains.
With the exception of the H3N2 strain, seroconversion rates (SCRs) among participants who received the subunit vaccine were significantly increased vs those who received the split-virion vaccine for the H1N1 (SCR, 82.71% vs 78.65%; P =.005), BV (SCR, 84.96% vs 81.08%; P =.005), and BY (SCR, 88.36% vs 81.96%; P <.001) strains.
This study was limited as the researchers did not assess participants with laboratory-confirmed influenza, nor did they assess cell-mediated immune responses following vaccination, including CD4+ and CD8+ T-cell responses. In addition, some participants had preexisting antibody responses.
In addition to demonstrating immunologic noninferiority to the split-virion vaccine, the subunit influenza vaccine was found to be “safe and well-tolerated” among individuals 3 years and older, the researchers concluded.
Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.
Zhang Y, Wang Y, Jia C, et al. Immunogenicity and safety of an egg culture-based quadrivalent inactivated nonadjuvanted subunit influenza vaccine in subjects 3 years: a randomized, multicenter, double-blind, active-controlled phase III, noninferiority trial. Vaccine. 2022;S0264-410X(22)00846-5. doi:10.1016/j.vaccine.2022.06.078