Immunogenicity of bivalent versus monovalent mRNA booster vaccination among adult paramedics in Canada who had received three prior mRNA wild-type doses

Asamoah-Boaheng M, Goldfarb DM, Kayda I, Yap J, Kirkham T, Karim ME, Demers PA, Copp JM, Grunau B. Immunogenicity of bivalent versus monovalent mRNA booster vaccination among adult paramedics in Canada who had received three prior mRNA wild-type doses. Access Microbiol. 2025;7(1):000791.v3. doi:10.1099/acmi.0.000791.v3

Introduction: Comparative immunogenicity from different mRNA booster vaccines (directed at WT, BA.1 or BA.4/5 antigens) remains unclear. 

Methods: We included blood samples from adult paramedics who received three mRNA WT-directed vaccines plus a fourth dose of the following: (1) WT monovalent, (2) Moderna BA.1-WT bivalent or (3) Pfizer BA.4/5 WT bivalent vaccine. The primary outcome was angiotensin-converting enzyme 2 (ACE2) inhibition to BA.4/5 antigen. We used optimal pair matching (using age, sex-at-birth, preceding SARS-CoV-2 infection and fourth vaccine-to-blood collection interval) to create balanced groups to individually compare each vaccine type to each other vaccine (overall, within subgroups defined by SARS-CoV-2 infection and after combining BA.1 and BA.4/5 cases). We compared outcomes with the Wilcoxon matched-pairs signed rank test.

Results: Overall, 158 paramedics (mean age 45 years) were included. ACE2 inhibition was higher for BA.1 compared to WT (P=0.002); however, no difference was detected between BA.4/5 vs. WT or BA.1 vs. BA.4/5. Among cases with preceding SARS-CoV-2, there were no detected between-group differences. Among cases without preceding SARS-CoV-2, the only detected difference was BA.1>WT (P=0.003). BA.1 and BA.4/5 cases combined had higher ACE2 inhibition than WT (P=0.003). 

Conclusion: Omicron-directed vaccines appear to improve Omicron-specific immunogenicity; however, this appears limited to SARS-CoV-2-naive individuals.