Introduction: The SARS-CoV-2 virus continue to evolve, with emerging variants increasingly capable of escaping immunity from prior vaccination or infection, contributing to ongoing transmission and recurrent waves of disease. COVID-19 vaccines protect against severe SARS-CoV-2 infection and death. They also provide modest short-term protection (≤3 months) against symptomatic SARS-CoV-2 infection. The durability and breadth of SARS-CoV-2 immunity after multiple boosters, particularly with respect to vaccine type and against emerging variants, remain uncertain. Addressing this knowledge gap is critical to inform optimal booster strategies and guide the development of next-generation COVID-19 vaccines.
Objectives: We report immunogenicity, safety and efficacy over 12 months following a fourth COVID-19 mRNA or protein vaccine dose.
Methods: Adults aged >18 years were randomised 1:1 to receive a bivalent mRNA vaccine (mRNA-1273.214/mRNA-1273.222, Moderna; n=177) or a protein vaccine (NVX-CoV-2373, Novavax; n=176). A self-selected control group (no fourth dose) were also recruited (n=143). Follow-up occurred at six- and 12-months post-vaccination. Geometric mean ratio (GMR) of anti-Spike binding IgG and surrogate neutralising antibodies to Ancestral and Omicron variants (BA.1, BA.4/5 and JN.1), and T-cell immunity using an IFN-γ-release assay (IGRA) were compared between the study groups.
Results: The IgG GMC against Ancestral strain were higher in the Moderna group than the Novavax group at six- (GMR: 1.59, 95% CI: 1.38-1.82) and 12-months post-vaccination (GMR: 1.34, 95% CI:1.16-1.55), and similarly for Omicron BA.1, BA.4/5 and JN.1 variants (six months: ranged from GMR: 1.62-1.66, 95% CI: 1.41-1.91; 12 months: ranged from GMR: 1.33-1.43, 95% CI: 1.15-1.67). Similar results for neutralising antibodies were also observed. However, no differences in IGRA were observed between Moderna and Novavax. The IgG GMCs against Ancestral strain and Omicron variants in both vaccine groups were higher than the control group at both timepoints (six months: ranged from GMR: 1.24-2.40, 95% CI: 1.04-2.86; 12 months: ranged from GMR: 1.04-1.62, 95% CI: 0.87-1.93). As a post-hoc analysis, 68.1% (94/138) in the control group had a SARS-CoV-2 infection over the 12-month period, compared with 43.0% (74/172) and 47.0% (77/164) in the Moderna and Novavax group, respectively.
Conclusions: While the bivalent Moderna vaccine induced higher immune responses than ancestral Novavax vaccine as a fourth dose, both vaccine groups appeared to provide comparable protection against SARS-CoV-2 Omicron variants over a 12-month period.