Safety and Immunogenicity of Omicron Protein Vaccines in mRNA-Vaccinated Adolescents: A Phase 3, Randomised Trial

Summary Objectives Safety and immunogenicity assessment of updated monovalent and bivalent SARS-CoV-2 vaccines in adolescents. Methods This phase 3, double-blinded study randomised 12–<18-year-old participants, who received ≥2 prior doses of an approved/authorised mRNA-based COVID-19 vaccine, 1:1 to receive NVX-CoV2601 (XBB.1.5) or a bivalent vaccine (NVX-CoV2373 [Wuhan] + NVX-CoV2601). The primary immunogenicity endpoint was day-28 neutralizing antibody (nAb) geometric mean titres (GMTs) against XBB.1.5. Safety endpoints were solicited reactogenicity ≤7 days and unsolicited adverse events (AEs) ≤28 days post vaccination and frequency/severity of predefined AEs of special interest through day 180. Results Of 401 randomised participants, nAb GMTs against XBB.1.5 increased (GMFR [95% CI]) for both NVX-CoV2601 (12.2 [9.5–15.5]) and the bivalent vaccine (8.4 [6.8–10.3]); post-vaccination responses to ancestral SARS-CoV-2 and the JN.1 variant were also observed. Increases in anti-spike IgG levels were comparable between the groups. Solicited and unsolicited AEs were mild to moderate, with similar occurrence among the groups. Severe and serious events were rare and unrelated to the study vaccines; no PIMMCs or myocarditis/pericarditis were reported. Conclusions NVX-CoV2601 elicited more robust antibody responses to XBB.1.5 and ancestral virus, compared with a bivalent formulation. The safety profile within each group was consistent with the prototype vaccine (NVX-CoV2373).