The impact of pre-existing immunity on mRNA booster doses of BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2

Researchers assessed the impact of pre-existing immunity on messenger ribonucleic acid (mRNA) booster doses of BNT162b2 and mRNA-1273 vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The impact of pre existing immunity on mRNA booster doses of BNT162b2 and mRNA-1273 vaccines against SARS CoV-2

Messenger ribonucleic acid (mRNA) vaccines have been reported to be highly effective in preventing coronavirus disease 2019 (COVID-19) severity but breakthrough infection cases, emerging SARS-CoV-2 strains, and waning of antibody titers warrant the need for booster doses Booster mRNA vaccinations have been implemented widely; however, the extent of influence on mRNA booster efficacy by existing/previous immunity is unclear. researchers assessed the impact of pre-booster anti-SARS-CoV-2 immunity (by vaccination or natural SARS-CoV-2 infection) on BNT162b2 and mRNA-1273 booster doses for COVID-19.

The study cohort comprised individuals who had received prime BNT162b2 or mRNA-1273 vaccination. First, the team investigated the effect of pre-existing immunity levels against the SARS-CoV-2 spike (S) antigen on the efficacy of mRNA booster vaccinations among SARS-CoV-2-negative individuals who had received single mRNA vaccinations previously. The antibody titers among singly vaccinated and previously SARS-CoV-2-exposed individuals were also assessed. Further, passive immunization analyses were performed to understand the impact of seropositivity on the mRNA booster immunogenicity. After three weeks of immunization, plasma cells were quantified by enzyme-linked immune absorbent spot (ELISPOT)-based assays.

In addition to the antibody titers, the pre-boost, and the post-boost antibody titers, the cluster of differentiation 8 (CD8) T lymphocyte counts were also compared. The enzyme-linked immunosorbent assays (ELISA) were performed to distinguish between antibodies derived from mice and humans. To further evaluate seropositivity effects on mRNA boosting efficacy, sera from five donor individuals (pre-vaccination vs. post-vaccination) were transferred into C57BL/6 mice. The mice also received mRNA prime SARS-CoV-2 ancestral strain vaccination the following day and a booster mRNA ancestral strain or Omicron strain vaccine dose after three weeks. In addition, after two weeks of the initial mRNA vaccination in mice, sera previously harvested in C57BL/6 mice were transferred to BALB/c mice. Antibodies from C57BL/6 mice and the BALB/c mice contained the immunoglobulin G (IgG)[b] allele and IgG[a] alleles, respectively.

Further, K18- hACE2 (host angiotensin-converting enzyme 2) mice were primed with an ancestral strain vaccine or an Omicron strain vaccine. After two weeks of prime vaccination, the mice were intranasally inoculated with 5×104 plaque-forming units (PFU) of Omicron. To investigate if seropositivity to SARS-CoV-2 antigens encoded by the mRNA vaccines could limit in situ antigen expression at the vaccination site after mRNA vaccination, mRNA-LNP luciferase (and Ad5-luciferase for comparison) vaccine platforms were used, which expressed the same antigen.

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