Immunogenicity and safety of a monovalent omicron XBB.1.5 SARS-CoV-2 recombinant spike protein vaccine as a heterologous booster dose in US adults: interim analysis of a single-arm phase 2/3 study

Authorities globally recommended a monovalent omicron XBB.1.5-based COVID-19 vaccine for the 2023-24 season. The Novavax COVID-19 vaccine, NVX-CoV2601, contains XBB.1.5 recombinant spike protein, based on an authorised prototype vaccine (NVX-CoV2373) technology. We aimed to determine whether a single dose of NVX-CoV2601 versus NVX-CoV2373 (from a previous study [2019nCoV-311 part 2]) produced superior neutralising antibody (nAb) responses, and non-inferior seroresponse rates to XBB.1.5, after three or more previous mRNA-based COVID-19 vaccinations.BACKGROUNDAuthorities globally recommended a monovalent omicron XBB.1.5-based COVID-19 vaccine for the 2023-24 season. The Novavax COVID-19 vaccine, NVX-CoV2601, contains XBB.1.5 recombinant spike protein, based on an authorised prototype vaccine (NVX-CoV2373) technology. We aimed to determine whether a single dose of NVX-CoV2601 versus NVX-CoV2373 (from a previous study [2019nCoV-311 part 2]) produced superior neutralising antibody (nAb) responses, and non-inferior seroresponse rates to XBB.1.5, after three or more previous mRNA-based COVID-19 vaccinations.In part 1 of this single-arm, phase 2/3 study (2019nCoV-313), participants aged 18 years or older who had been previously vaccinated with three or more doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) were enrolled across 30 US centres (research groups and universities) located across 20 states. Participants received one intramuscular injection of NVX-CoV2601 (5 μg XBB.1.5 spike plus 50 μg Matrix-M adjuvant). Coprimary endpoints were superiority of baseline-adjusted nAb geometric mean XBB.1.5 titres (adjusted GMTs), with superiority declared when the lower bound of the 95% CI for the GMT ratio (GMTR) was greater than 1, and non-inferiority of seroresponse rates, with non-inferiority declared when the lower bound of the 95% CI for the seroresponse rate difference was greater than -10%, on day 28; comparisons were made for NVX-CoV2601 administered in this study versus NVX-CoV2373 administered in part 2 (group G) of the 2019nCoV-311 study. Coprimary endpoints were assessed in the per-protocol immunogenicity set (ie, all participants who received study vaccine, underwent 28 days of follow-up, had day 0 and day 28 samples available, and had no major protocol deviations). Safety was a secondary endpoint and included assessments of solicited treatment-emergent adverse events up to 7 days and unsolicited treatment-emergent adverse events up to 28 days after