Real-world evaluation of 2023–2024 XBB.1.5 mRNA and protein-based COVID-19 vaccine reactogenicity from the randomized BEEHIVE trial

Abstract

ABSTRACT The objective of this analysis was to assess reactogenicity profile differences between a protein- and mRNA-based COVID-19 vaccine in participants who had previously received ≥2 doses of an mRNA-based vaccine in a real-world, double-blinded, randomized, controlled trial. In the BEEHIVE/NCT06065176 trial (ClinicalTrials.gov: NCT06065176), participants randomized 1:1 received one dose of the Novavax (NVX) or Pfizer–BioNTech (PFZ) COVID-19 vaccine 2023–2024 formulation (XBB.1.5); a comparator group did not receive a dose. Electronic surveys collected solicited systemic (fatigue, fever, headache, joint pain, malaise/feeling sick, muscle pain, and nausea/vomiting) and local (injection-site pain, tenderness, and swelling) events on days 1, 2, and 6 after study vaccination. Significantly lower proportions of participants in the NVX (n = 448) vs. PFZ (n = 453) group reported a systemic (62.1% vs. 75.7%; risk difference −13.7%, 95% CI: −19.6% to −7.7%) or local (81.0% vs. 92.7%; risk difference −11.7%, 95% CI: −16.0% to −7.3%) event in the day-1 survey (both Cochran–Mantel–Haenszel P < .0001). Most events were mild. Reactogenicity rates decreased throughout the week; >80% and >94% of participants in either group reported no systemic or local reactogenicity, respectively, in the day-6 survey. Mean number of events/person were significantly lower for the NVX vs. PFZ group in the day-1 (systemic and local) and day-2 (local) surveys (each P < .0001). There were significant differences in reactogenicity profiles for the 2023–2024 formulations of the NVX and PFZ COVID-19 vaccines, with NVX consistently associated with lower reactogenicity rates than PFZ.