P-607. Immunogenicity and Tolerability of the Novavax Nanoparticle Influenza Vaccine (NIV) and COVID-Influenza Combination Vaccine (CIC)

Abstract Background There is a public health need for annual immunizations against both SARS-CoV-2 and influenza viruses. We developed both a standalone saponin-adjuvanted (Matrix-M™) recombinant quadrivalent hemagglutinin (HA) nanoparticle influenza vaccine (qNIV), and a COVID and influenza combination (CIC) vaccine, comprising recombinant SARS-CoV-2 Spike (rS) (NVX-CoV2373), qNIV, and Matrix-M adjuvant.Table 1.Study design Methods Participants in Australia and New Zealand (1571 treated, including 864 in the CIC group) aged 50–80 years were randomized equally to receive one intramuscular dose of vaccine in 1 of 20 groups: either 1 of 11 different dose/formulations of CIC, 1 of 3 formulations of qNIV with Matrix-M, 1 of 4 formulations of standalone rS with Matrix-M, or 1 of 2 influenza vaccine comparators (Fluzone HD® or FLUAD®) (Table 1). Immunogenicity assessments included anti-spike IgG, SARS-CoV-2 neutralizing antibody (vaccine-homologous and -heterologous strains), wild-type influenza HAI antibodies (vaccine-homologous strains). Reactogenicity was assessed for 7 days following vaccination and SAEs, AESIS, and MAAEs were assessed throughout the study.Table 2.CIC and qNIV post-vaccination immunogenicity assessments (Day 21, per-protocol analysis set) Results qNIV ([HA60/M75], n=75) HAI and neutralizing antibody responses were significantly higher than FLUAD and Fluzone HD against both vaccine-homologous A strains, particularly against H3N2 (Table 2). CIC ([HA60/rS35/M75], n=75) showed evidence of rS and HA antigen interference, but achieved anti-spike IgG and influenza HAI antibody responses that were comparable to both the standalone rS vaccine (NVX-CoV2373) and FLUAD /Fluzone HD, respectively (Table 2). All qNIV and CIC formulations evoked local and systemic solicited adverse events at rates and severities less than or comparable to FLUAD and Fluzone HD (Figure 1). There was no dose dependence of HA, rS antigens, or Matrix-M on tolerability. SAEs were infrequent in all groups.Figure 1.Solicited (A) local and (B) systemic TEAEs within 7 days of vaccination (safety analysis population) Conclusion qNIV produced improved wild-type HAI antibody responses as compared to FLUAD and Fluzone HD against influenza A strains, notably against H3N2. CIC achieved both anti-spike IgG responses comparable to the authorized prototype NVX-CoV2373 rS vaccine and HAI responses comparable to licensed enhanced influenza comparators. CIC and qNIV had safety profiles comparable to Fluzone HD and FLUAD. Disclosures Vivek Shinde, MD, MPH, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Joyce S. Plested, n/a, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Tim Vincent, n/a, Novavax, Inc.: Employee|Novavax, Inc.: Stocks/Bonds (Public Company) Mingzhu Zhu, n/a, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Shane Cloney-Clark, n/a, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Zhaohui Cai, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Bridget Riviers, Ph.D., Novavax, Inc.: Employee|Novavax, Inc.: Stocks/Bonds (Public Company) Farnaz Mahkhou, Ph.D., Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Anthony M. Marchese, PhD, Novavax Inc: Employee|Novavax Inc: Stocks/Bonds (Public Company) Iksung Cho, MS, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Louis F. Fries, III, MD, Novavax, Inc.: contractor for Novavax|Novavax, Inc.: Stocks/Bonds (Public Company) Wayne Woo, MS, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company)