Immunogenicity and efficacy over 12 months following a fourth dose of a bivalent mRNA or protein-based COVID-19 vaccine: A randomised controlled trial in Australia

Abstract

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) was also recruited (n=143). Follow-up occurred at six- and 12-months post-vaccination. Geometric mean concentrations (GMCs) of anti-Spike binding IgG and surrogate neutralising antibodies to Ancestral and Omicron variants (BA.1, BA.4/5 and JN.1), and IFN-γ concentrations (IGRA) as a proxy for T cell immunity were compared between the study groups.

Results: The IgG levels against Ancestral strain were higher in the Moderna group than the Novavax group at six- [Geometric mean ratio (GMR): 1.59, 95% CI: 1.38 to 1.82] and 12-months post-vaccination (GMR: 1.34, 95% CI:1.16 to 1.55), and similarly for Omicron BA.1, BA.4/5 and JN.1 variants (six months: ranged from GMR: 1.62 to 1.66, 95% CI: 1.41 to 1.91; 12 months: ranged from GMR: 1.33 to 1.43, 95% CI: 1.15 to 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 to 2.40; 12 months: ranged from GMR: 1.04 to 1.62). 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 the Ancestral Novavax vaccine as a fourth dose, both vaccines appeared to provide comparable protection against SARS-CoV-2 Omicron variants over 12-months.

Keywords: Antibody; Booster; COVID-19; Fourth dose; Immunity; SARS-CoV-2; Vaccination.