Whereas, when neutralizing antibody responses were assessed against egg-adapted A/Singapore/INFIMH-16-0019/2016 (H3N2) virus, both vaccines appeared to perform comparably (Supplementary Figure 1). participants were randomized, immunized, and followed for safety and immunogenicity. Matrix-Madjuvanted qNIV induced superior wt-HAI antibody responses against 5 of 6 homologous or drifted strains compared with 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 g Matrix-M adjuvant induced substantially higher post-vaccination geometric mean fold increases of influenza HA-specific polyfunctional CD4+ T cells compared with IIV3-HD or RIV4. Overall, similar frequencies of solicited and unsolicited adverse events were reported in all treatment groups. == Conclusions == qNIV with 75 g 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. == Clinical Trials Registration == NCT03658629. Keywords:influenza, vaccination, hemagglutination inhibition, PD1-PDL1 inhibitor 1 cell-mediated immunity We compared multiple formulations of a recombinant Matrix-Madjuvanted nanoparticle influenza vaccine with 2 licensed vaccines in older adults. The nanoparticle vaccine was well tolerated and induced hemagglutination-inhibition antibody and CD4+ T-cell responses to vaccine-homologous and drifted A/H3N2 influenza viruses. Seasonal influenza vaccination has been the cornerstone of prevention efforts to address the substantial health PD1-PDL1 inhibitor 1 and economic burdens of influenza [1,2]. However, recent developments, including several severe A(H3N2)-predominant influenza seasons; recurrent reports of poor field vaccine effectiveness from Europe, Canada, and the United States; the increasingly recognized risk of antigenic mismatch arising from egg-based vaccine production; and the mounting PD1-PDL1 inhibitor 1 challenge of predicting which viruses will circulate in the face of increasing strain diversity, have undermined confidence in available influenza vaccines and reignited calls for developing improved, broadly cross-protective influenza vaccines [319]. These challenges have been acutely represented by contemporary circulating influenza A(H3N2) viruses because of their rapid rate of genetic and antigenic evolution, increased susceptibility to egg-adaptive mutations, and because they account for the majority of influenza-attributable morbidity and mortality [17,2022]. Additional challenges PD1-PDL1 inhibitor 1 to overcome include potential modulatory effects of early-life immunological imprinting on vaccine effectiveness, limited durability of vaccine-induced protective immune responses, and limited induction of cellular immunity [4,7,2325]. We recently described the development of a novel saponin (Matrix-M)-adjuvanted recombinant hemagglutinin (HA) trivalent nanoparticle influenza vaccine (tNIV) produced in a Sf9 insect cell/recombinant baculovirus system that retains fidelity to wild-type (wt) circulating virus HA sequences and contains conserved epitopes that stimulate broadly neutralizing antibodies (bnAbs) [26,27]. In a phase 1 study, tNIV demonstrated improved induction of wild-type hemagglutination inhibition (wt-HAI) antibody titers against A/H3N2 drift variants isolated over a 5-year period compared with an egg-derived, trivalent high-dose inactivated influenza vaccine (IIV3-HD) [28]. In the present phase 2 study, we further evaluated the safety and immunogenicity of various doses and formulations of quadrivalent NIV (qNIV) in adults aged 65 years, with or without Matrix-M adjuvant, compared with 2 currently licensed influenza vaccines for which enhanced efficacy relative to standard IIV has been reported Rabbit Polyclonal to FMN2 (IIV3-HD and quadrivalent recombinant HA influenza vaccine [RIV4]) [25]. == METHODS == == Study Design == This randomized, observer-blind, comparator-controlled, dose and formulation optimization trial enrolled 1375 clinically stable adults aged 65 years across 14 US sites from 24 September 2018 to 19 October 2018. Eligible participants were randomized into 1 of 7 treatment groups, stratified by age (60 to <75 and 75 years), gender, and receipt of 20172018 seasonal influenza vaccine (Figure 1;Supplementary Table 1). Inclusion and exclusion criteria are detailed in theSupplementary Appendix. == Figure 1. == Flow diagram on screening, enrollment, and disposition of participants through the study. Safety population is defined as all participants who provided consent, were randomized, and received any investigational treatment; used for all descriptive safety analyses. Immunogenicity per protocol population is defined as all participants in the safety population who received the assigned investigational treatment according to the protocol, had wild-type hemagglutination inhibition (HAI) serology results for day 0 and day 28, and had no major protocol deviations that affected.
Whereas, when neutralizing antibody responses were assessed against egg-adapted A/Singapore/INFIMH-16-0019/2016 (H3N2) virus, both vaccines appeared to perform comparably (Supplementary Figure 1)