We developed a recombinant quadrivalent hemagglutinin (HA) saponin-adjuvanted (Matrix-MTM) nanoparticle influenza vaccine (qNIV) to address gaps in current influenza vaccines, and a COVID-Influenza Combination (CIC) vaccine, comprising recombinant SARS-CoV-2 Spike (rS) and qNIV, for the future need to vaccinate against influenza and SARS-CoV-2.
In the influenza Phase 3, we randomized 2652 participants aged ≥65 years 1:1 to receive a dose of qNIV or quadrivalent inactivated influenza vaccine (IIV4).
In the Phase 1/2 CIC dose-finding trial, seropositive (COVID-19 vaccinated ³ 8 weeks prior) participants (N=642) aged 50-70 years were randomized equally, to receive two doses, 56 days apart, to 1 of 14 different dose/formulations of CIC using a design-of-experiments approach (dose range: rS 2.5-22.5ug, HA 5-60ug; 50ug Matrix-M), or to 1 of 2 reference formulations of either standalone rS with Matrix-M [2 doses] or qNIV with Matrix-M [1 dose ]. Multiple regression was used to create predictive models to assess dose optimization.
In the Phase 3, qNIV induced higher post-vaccination (Day 28) wild-type HAI antibody responses than IIV4 against four vaccine-homologous strains (24-66% increased) and six drifted A(H3N2) strains (34-46% increased) representing multiple antigenically distinct clades/subclades. Wild-type neutralizing antibody responses produced a similar pattern. qNIV induced potent post-vaccination (Day7) polyfunctional antigen-specific effector CD4+ T-cell responses (126-189% higher compared to IIV4). qNIV had a safety profile comparable to IIV4.
In the CIC trial, all formulations were well-tolerated, with a reactogenicity/safety profile generally comparable to standalone rS or qNIV. Regression modelling of dose responses revealed that both rS and HA antigens in a CIC formulation modestly interfered with each other, however, interference was overcome with dose adjustment.
qNIV produced qualitatively and quantitatively enhanced immune responses, addressing several challenges confronting current egg-derived seasonal influenza vaccines.
CIC formulations were well-tolerated and immunogenic, with various dose combinations achieving response comparable to standalone rS and qNIV vaccines.