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

Introduction: Comparative immunogenicity from different mRNA booster vaccines (directed at wild-type [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: (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 (ACE-2) 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 Wilcoxon matched pairs signed rank test. Results Overall, 158 paramedics (mean age 45 years) were included. ACE-2 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 between-group differences. Among cases without preceding SARS-CoV-2, the only 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-naïve individuals.