COVID-19 Adenoviral Vector Vaccination Elicits a Robust Memory B Cell Response with the Capacity to Recognize Omicron BA.2 and BA.5 Variants.

Following the COVID-19 pandemic, novel vaccines have successfully reduced severe disease and death. Despite eliciting lower antibody responses, adenoviral vector vaccines are nearly as effective as mRNA vaccines. Therefore, protection against severe disease may be mediated by immune memory cells. We here evaluated plasma antibody and memory B cells (Bmem) targeting the SARS-CoV-2 Spike receptor-binding domain (RBD) elicited by the adenoviral vector vaccine ChAdOx1 (AstraZeneca), their capacity to bind Omicron subvariants, and compared this to the response to mRNA BNT162b2 (Pfizer-BioNTech) vaccination. Whole blood was sampled from 31 healthy adults pre-vaccination and 4 weeks after dose one and dose two of ChAdOx1. Neutralizing antibodies (NAb) against SARS-CoV-2 were quantified at each time point. Recombinant RBDs of the Wuhan-Hu-1 (WH1), Delta, BA.2, and BA.5 variants were produced for ELISA-based quantification of plasma IgG and incorporated separately into fluorescent tetramers for flow cytometric identification of RBD-specific Bmem. NAb and RBD-specific IgG levels were over eight times lower following ChAdOx1 vaccination than BNT162b2. In ChAdOx1-vaccinated individuals, median plasma IgG recognition of BA.2 and BA.5 as a proportion of WH1-specific IgG was 26% and 17%, respectively. All donors generated resting RBD-specific Bmem, which were boosted after the second dose of ChAdOx1 and were similar in number to those produced by BNT162b2. The second dose of ChAdOx1 boosted Bmem that recognized VoC, and 37% and 39% of WH1-specific Bmem recognized BA.2 and BA.5, respectively. These data uncover mechanisms by which ChAdOx1 elicits immune memory to confer effective protection against severe COVID-19.

Humoral immunity and B-cell memory in response to SARS-CoV-2 infection and vaccination.

Natural infection with SARS-CoV-2 induces a robust circulating memory B cell (Bmem) population, which remains stable in number at least 8 months post-infection despite the contraction of antibody levels after 1 month. Multiple vaccines have been developed to combat the virus. These include two new formulations, mRNA and adenoviral vector vaccines, which have varying efficacy rates, potentially related to their distinct capacities to induce humoral immune responses. The mRNA vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) elicit significantly higher serum IgG and neutralizing antibody levels than the adenoviral vector ChAdOx1 (AstraZeneca) and Ad26.COV2.S (Janssen) vaccines. However, all vaccines induce Spike- and RBD-specific Bmem, which are vital in providing long-lasting protection in the form of rapid recall responses to subsequent infections. Past and current SARS-CoV-2 variants of concern (VoC) have shown the capacity to escape antibody neutralization to varying degrees. A booster dose with an mRNA vaccine following primary vaccination restores antibody levels and improves the capacity of these antibodies and Bmem to bind viral variants, including the current VoC Omicron. Future experimental research will be essential to evaluate the durability of protection against VoC provided by each vaccine and to identify immune markers of protection to enable prognostication of people who are at risk of severe complications from COVID-19.