SARS-CoV-2 mRNA Vaccines Elicit Different Responses in Immunologically Naïve and Pre-Immune Humans

Abstract

As the COVID-19 pandemic continues, the authorization of vaccines for emergency use has been crucial in slowing down the rate of infection and transmission of the SARS-CoV-2 virus that causes COVID-19. In order to investigate the longitudinal serological responses to SARS-CoV-2 natural infection and vaccination, a large-scale, multi-year serosurveillance program entitled SPARTA (SARS SeroPrevalence and Respiratory Tract Assessment) was initiated at 4 locations in the U.S. The serological assay presented here measuring IgG binding to the SARS-CoV-2 receptor binding domain (RBD) detected antibodies elicited by SARS-CoV-2 infection or vaccination with a 95.5% sensitivity and a 95.9% specificity. We used this assay to screen more than 3100 participants and selected 20 previously infected pre-immune and 32 immunologically naïve participants to analyze their antibody binding to RBD and viral neutralization (VN) responses following vaccination with two doses of either the Pfizer-BioNTech BNT162b2 or the Moderna mRNA-1273 vaccine. Vaccination not only elicited a more robust immune reaction than natural infection, but the level of neutralizing and anti-RBD antibody binding after vaccination is also significantly higher in pre-immune participants compared to immunologically naïve participants (p<0.0033). Furthermore, the administration of the second vaccination did not further increase the neutralizing or binding antibody levels in pre-immune participants (p=0.69). However, ~46% of the immunologically naïve participants required both vaccinations to seroconvert.

Limited Impact of Delta Variant’s Mutations on the Effectiveness of Neutralization Conferred by Natural Infection or COVID-19 Vaccines in a Latino Population

“…Consistent with other studies [34,36,37], our data confirm that subjects previously exposed to SARS-CoV-2 reach levels of protection against all tested variants after just one vaccine dose. Furthermore, we found a limited contribution, if any, of a second vaccine dose in pre-exposed individuals.…”

Comparison of Antibody Response Durability of mRNA-1273, BNT162b2, and Ad26.COV2.S SARS-CoV-2 Vaccines in Healthcare Workers

“…Other studies have also shown higher antibody responses in previously COVID-19 infected vs. naive individuals with both mRNA vaccines. 4,46,47 This is one of the first comparative COVID-19 vaccine immunologic durability studies; our results are consistent with results from two other studies (below). 3,35 A synopsis of the current literature shows many more studies reporting antibody and VE results for individual vaccines rather than comparative analyses.…”

The effect of waning on antibody levels and memory B cell recall following SARS-CoV-2 infection or vaccination

“…Viral neutralization (VN) assays were performed in a Biosafety Level 3 (BSL-3) laboratory as previously described 10 . The USA-WA1/2020 SARS-CoV-2 strain (100 TCID50/50µl; NCBI accession number: PRJNA717311) was co-incubated with serially diluted serum samples for 1 hour at 37°C and then added to a monolayer of Vero E6 cells.…”

“…Anti-spike antibodies increase significantly following vaccination 10,11 . However, there is a significant drop in antibody levels within the first few months following vaccination [12][13][14] .…”