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

Comparative immunogenicity from different mRNA booster vaccines (directed at WT, BA.1 or BA.4/5 antigens) remains unclear. 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. Overall, 158 paramedics (mean age 45 years) were included. ACE2 inhibition was higher for BA.1 compared to WT (=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 (=0.003). BA.1 and BA.4/5 cases combined had higher ACE2 inhibition than WT (=0.003). Omicron-directed vaccines appear to improve Omicron-specific immunogenicity; however, this appears limited to SARS-CoV-2-naive individuals.