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.

The coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus has rapidly evolved since late 2019 due to highly transmissible Omicron variants. While most Canadian paramedics have received COVID-19 vaccination the optimal ongoing vaccination strategy is unclear. We investigated neutralizing antibody (NtAb) response against wild-type (WT) Wuhan Hu-1 and Omicron BA.4/5 lineages based on the number of doses and past SARS-CoV-2 infection at 18 months post initial vaccination (with a Wuhan Hu-1 platform mRNA vaccine [BNT162b2 or mRNA-1273}). Demographic information previous COVID-19 vaccination infection history and blood samples were collected from paramedics 18 months post initial mRNA COVID-19 vaccine dose. Outcome measures were ACE2 percent inhibition against Omicron BA.4/5 and WT antigens. We compared outcomes based on number of vaccine doses (two vs. three) and previous SARS-CoV-2 infection status using the Mann-Whitney U test. Of 657 participants the median age was 40 years (IQR 33-50) and 251 (42%) were females. Overall median percent inhibition to BA.4/5 and WT was 71.61% (IQR 39.44-92.82) and 98.60% (IQR 83.07-99.73) respectively. Those with a past SARS-CoV-2 infection had a higher median percent inhibition to BA.4/5 and WT when compared to uninfected individuals overall and when stratified by two or three vaccine doses. When comparing two vs. three WT vaccine doses among SARS-CoV-2 negative participants we did not detect a difference in BA.4/5 percent inhibition but there was a difference in WT percent inhibition. Among those with previous SARS-CoV-2 infection(s) when comparing two vs. three WT vaccine doses there was no observed difference between groups. These findings demonstrate that additional Wuhan Hu-1 platform mRNA vaccines did not improve NtAb response to BA.4/5 but prior SARS-CoV-2 infection enhances NtAb response.

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.