Phase 2/3 open-label study on NVX-CoV-2601 (XBB.1.5) vaccine in previously COVID-19 mRNA vaccinated and vaccine-naive participants: a 6-month follow-up

BackgroundSeasonal (2023-2024) COVID-19 vaccine recommendations included updates against Omicron XBB.1.5. NVX-CoV2601 contains XBB.1.5 recombinant spike (rS) protein, Matrix-M adjuvant, and is based on authorized prototype vaccine (NVX-CoV2373) technology. Immunogenicity and safety outcomes 6 months after vaccination following a single dose of monovalent NVX-CoV2601 in previously vaccinated and vaccine-naive participants aged [≥]18 years are reported here. MethodsThe phase 2/3 open-label, single-arm 2019nCoV-313 study consisted of two parts (part 1: participants with [≥]3 prior mRNA vaccines; part 2: unvaccinated participants with a clinical history of COVID-19). Participants received a single dose of NVX-CoV2601. Primary endpoint analyses through day 28 were previously published. This final analysis assessed immunogenicity and safety through the end of the study (day 180). Immunogenicity data (e.g., neutralizing antibodies [nAbs] and anti-rS IgG antibodies) were summarized using geometric mean antibody levels and fold rise and seroresponse rate (SRR). ResultsThe safety analysis set included 332 participants in part 1 and 338 participants in part 2. In previously vaccinated participants, nAb geometric mean titers (GMTs; 95% CIs) were 120.7 (101.5-143.6) at day 0, increased to 955.5 (814.0-1121.4) at day 28, and decreased to 454.8 (382.9-540.3) at day 180. SRR decreased from 64.3% at day 28 to 41.1% at day 180. Similar results were seen in vaccine-naive participants, with GMTs of 67.0 (56.6-79.3), 1296.7 (1082.6-1553.2), and 303.6 (258.5-356.4) at day 0, 28, and 180, respectively. SRR waned from 74.3% at day 28 to 45.0% at day 180. Anti-rS IgG responses similarly increased at day 28 and had moderate decreases at day 180 in both groups. No new safety signals were reported. ConclusionsA single dose of NVX-CoV2601 showed robust, durable immunogenicity in both previously vaccinated and vaccine-naive adult participants. These data support the use of NVX-CoV2601 in both populations. Trial registrationNCT05975060 HighlightsO_LISingle-dose XBB.1.5-based vaccine, NVX-CoV2601, was well-tolerated C_LIO_LINVX-CoV2601 elicited robust immunogenicity, regardless of prior vaccination status C_LIO_LIImmune responses waned over time but remained well above baseline C_LI