SARS-CoV-2 ANTIBODY RESPONSES in INDIVIDUALS FOLLOWING mRNA BOOSTER VACCINATION

ABSTRACT

Background: Two years after its onset, the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains difficult to control despite the availability of several vaccines. Progress in controlling the pandemic is complicated by the emergence of variants with antibody-resistance. Methods: Here we report on the evolution of antibody and memory B cell responses in a cohort of SARS-CoV-2 naïve individuals who received two doses of the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines against SARS-CoV-2 and were boosted with a third mRNA vaccine dose thereafter. Results: Plasma neutralizing antibody titers in individuals vaccinated with two mRNA vaccines doses decrease over time, but can be restored by a third, i.e., a booster dose. A third vaccine dose also results in dramatically increased plasma neutralizing activities against viral variants, including the delta and omicron variants. Boosting vaccinated individuals also increases the number of RBD-specific memory B cells, which display clonal turnover after the third dose of the vaccine. The mononclonal antibodies generated by those cells have greater somatic hypermutation and increased neutralizing activity when compared to antibodies generated after the second dose, indicative of continued evolution of the humoral response to SARS-CoV-2. A substantial fraction of the monoclonal antibodies isolated after the third dose of an mRNA vaccine are able to neutralize pseudoviruses representing the delta and omicron variants, at low antibody concentrations. Conclusion: The data suggest that boosting vaccinated individuals with mRNA vaccines provides dramatically increased and broadened plasma neutralizing activity. This is the result of antibody evolution and the consequent production of potent and broadly active neutralizing antibodies.