Immunogenicity of Non-Egg-Based Influenza Vaccines in Sequential Vaccination Trial

A randomized open-label trial conducted during the 2018-19 and 2019-20 influenza seasons found that recombinant influenza vaccine (RIV) elicited superior immune responses against A/H3N2 viruses compared with cell culture-based (ccIIV) and egg-based inactivated influenza vaccines (IIV).

Influenza A/H3N2 poses a public health challenge due to its rapid antigenic evolution and reduced vaccine effectiveness linked to egg-based manufacturing methods. RIV and ccIIV, which are not produced using egg propagation, may overcome some of these limitations. However, limited evidence exists comparing their immunogenicity during consecutive vaccination seasons. This study aimed to fill that gap, focusing on antibody responses to cell-grown and egg-adapted A/H3N2, A/H1N1, and influenza B strains.

The study enrolled 373 participants aged 18 to 64 years, with 332 completing revaccination in the second season, to evaluate the immunogenicity of these vaccines when administered sequentially during 2 years. Participants were randomized to receive RIV, ccIIV, or IIV. Serum samples collected pre- and post-vaccination were tested using hemagglutination inhibition assays. Immunogenicity endpoints included geometric mean titers (GMT), mean fold rise, and seroconversion rates.

The study found that RIV generated significantly higher post-vaccination GMTs against the cell-grown 3C.2a A/H3N2 virus in both seasons compared to ccIIV and IIV (2018–19: P = .001; 2019–20: P = .001 for RIV vs ccIIV, P = .03 for RIV vs IIV). RIV also elicited stronger backboosting to the antigenically distinct 3C.2a virus from the prior season (GMT: 126 for RIV vs 71 for IIV and 55 for ccIIV in 2019–20). Antibody responses to A/H1N1 and type B strains were similar across all vaccine arms.

The study’s limitations include a lack of racial and ethnic diversity, a laboratory error that reduced sample size for influenza B serology in 2019-20, and the absence of data on hemagglutinin stalk-specific antibody responses.

“These results add to the growing evidence that recombinant influenza vaccines elicit a superior immunologic response to H3N2 viruses compared to other licensed vaccines,” the study authors concluded.

Reference

Boyce TG, Levine MZ, McClure DL, et al. Antibody response to sequential vaccination with cell culture, recombinant, or egg-based influenza vaccines among U.S. adults. Hum Vaccin Immunother. 2024;20(1):2370087. doi:10.1080/21645515.2024.2370087