Shinde V, Cai R, Plested J, Cho I, Fiske J, Pham X. Induction of Cross-reactive Hemagglutination Inhibiting Antibody and Polyfunctional CD4+ T-cell Responses by a Recombinant Matrix-M-Adjuvanted Hemagglutinin Nanoparticle Influenza Vaccine. Clin Infect Dis. 2020 Nov 4:ciaa1673
Methods: We conducted a randomized, observer-blind, comparator-controlled (trivalent high-dose inactivated influenza vaccine [IIV3-HD], or quadrivalent recombinant influenza vaccine [RIV4]), safety and immunogenicity trial of qNIV (in 5 different doses/formulations) in healthy adults aged ≥65 years. Vaccine immunogenicity was measured by hemagglutination-inhibition assays using reagents expressing wild-type HA sequences (wt-HAI) and cell-mediated immune (CMI) responses.
Results: A total of 1375 participants were randomized, immunized, and followed for safety and immunogenicity. Matrix-M-adjuvanted qNIV induced superior wt-HAI antibody responses against 5 of 6 homologous or drifted strains evaluated compared to unadjuvanted qNIV. Adjuvanted qNIV induced post-vaccination wt-HAI antibody responses at Day 28 that were: statistically higher than IIV3-HD against a panel of homologous or drifted A/H3N2 strains; similar to IIV3-HD against homologous A/H1N1 and B (Victoria) strains; and similar to RIV4 against all homologous and drifted strains evaluated. The qNIV formulation with 75 μg Matrix-M adjuvant induced substantially higher post-vaccination geometric mean fold-increases of influenza HA-specific polyfunctional CD4+ T-cells compared to IIV3-HD or RIV4. Overall, similar frequencies of solicited and unsolicited adverse events (AEs) were reported in all treatment groups.
Conclusions: qNIV with 75 μg Matrix-M adjuvant was well tolerated and induced robust antibody and cellular responses, notably against both homologous and drifted A/H3N2 viruses. Further investigation in a pivotal phase 3 trial is underway.
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