Relative Antibody Mediated Protection against Influenza in Vaccinated Children

Abstract

Charlotte Switzer47773*, Chris P Verschoor47774, Eleanor Pullenayegum47775, Pardeep Singh47776 and Mark Loeb47777

Background: Adjuvanted influenza vaccine has been shown to elicit more robust vaccine immunogenicity, as measured by the Hemagglutination Inhibition (HAI) assay. Post-vaccination HAI titers are the accepted correlate of protection against influenza. However, the proportion of relative vaccine protection in adjuvanted vaccines that is mediated by increased HAI titers has not been investigated.

Methods: A cluster randomized controlled trial of influenza vaccines in Canadian Hutterite colonies was conducted from the 2016-2017 to the 2018-2019 influenza season. Children were vaccinated with either Quadrivalent Inactivated Influenza Vaccine (QIV), or the MF59 adjuvanted trivalent influenza vaccine (aTIV). Sera were collected prior to and four weeks after vaccination, and HAI titers against A/H3N2 vaccine antigens were measured. We tested for differences in the hazard rate of influenza A/H3N2 infection using Cox proportional hazards models, and the proportion of relative vaccine protection in adjuvanted vaccinees mediated by higher HAI titers was estimated using a causal mediation model.

Results: Antibody titers from 542 paired serum samples were available, with 32 laboratory-confirmed influenza infections. Most infections were due to A/ H3N2 and occurred during a season of antigenic mismatch in the vaccine. Of 22 A/H3N2 infections, two occurred in the aTIV group (0.8%), versus 20 in the QIV group (6.6%). We estimated the relative adjuvanted vaccine efficacy against A/H3N2 as 87.8% (95% CI: 43.6%, 97.4%). The rise in post-vaccination titers in adjuvanted vaccinees explained 9.0% of vaccine protection, relative to quadrivalent controls.

Conclusion: Relative vaccine protection in adjuvanted vaccinees is not conclusively mediated by the superior induction of HAI titers. Adjuvanted vaccine effectiveness may be attributable to other mechanisms, such as increased engagement of the innateor cell-mediated immune repertoire. As most cases occurred during an antigenically mismatched season, adjuvanted vaccine protection against heterologous strains of influenza may be driven by cellular immunity, and further work is required.