RESULTS:

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.

Background. We examined the 11 month longitudinal antibody decay among two-dose mRNA vaccinees and identified factors associated with faster decay.

Methods. The study included samples from the COVID-19 Occupational Risk Seroprevalence and Immunity among Paramedics (CORSIP) longitudinal observational study of paramedics in Canada. Participants were included if they had received two mRNA vaccines without prior SARS-CoV-2 infection and provided two blood samples post-vaccination. The outcomes of interest were quantitative SARS-CoV-2 antibody concentrations. We employed spaghetti and scatter plots (with kernel-weighted local polynomial smoothing curve) to describe the trend of the antibody decay over 11 months post-vaccine and fit a mixed effect exponential decay model to examine the loss of immunogenicity and factors associated with antibody waning over time.

Results. This analysis included 652 blood samples from 326 adult paramedics. Total anti-spike antibody levels peaked on the twenty-first day (antibody level 9042 U ml−1) after the second mRNA vaccine dose. Total anti-spike antibody levels declined thereafter with a half-life of 94 [95 % CI: 70 143] days with levels plateauing at 295 days (antibody level 1021 U ml−1). Older age vaccine dosing interval <35 days and the BNT162b2 vaccine (compared to mRNA-1273 vaccine) were associated with faster antibody decay.

Conclusion. Antibody levels declined after the initial mRNA series with a half-life of 94 days plateauing at 295 days. These findings may inform the timing of booster vaccine doses and identifying individuals with faster antibody decay.