PT  - JOURNAL ARTICLE
AU  - Gemma E. Hartley
AU  - Emily S.J. Edwards
AU  - Nirupama Varese
AU  - Irene Boo
AU  - Pei M. Aui
AU  - Scott J. Bornheimer
AU  - P. Mark Hogarth
AU  - Heidi E. Drummer
AU  - Robyn E. O’Hehir
AU  - Menno C. van Zelm
TI  - Double-dose mRNA vaccination to SARS-CoV-2 progressively increases recognition of variants-of-concern by Spike RBD-specific memory B cells
AID  - 10.1101/2022.08.03.502703
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.08.03.502703
4099  - http://biorxiv.org/content/early/2022/08/04/2022.08.03.502703.short
4100  - http://biorxiv.org/content/early/2022/08/04/2022.08.03.502703.full
AB  - Background SARS-CoV-2 vaccination with BNT162b2 (Pfizer BioNTech) has been shown to be 95% effective.1 Double-dose vaccination generates high levels of spike-specific antibodies, memory B cells (Bmem) and T cells. However, variants of concern (VoC) with mutations in the spike Receptor Binding Domain (RBD) can evade antibody responses. Booster vaccinations improve antibody recognition of VoC, but it is unclear if this is due to higher total antibodies or their capacity to bind VoC. We here addressed the capacity of surface Ig on single Wuhan-specific Bmem after first and second dose BNT162b2 vaccination to recognize variant RBD.Methods Samples were collected from 30 healthy COVID-19 naive individuals pre-BNT162b2 vaccination, 3 weeks post-dose 1 and 4-weeks post-dose 2. Plasma antibodies and Bmem were evaluated using recombinant RBD proteins of the Wuhan, Gamma and Delta strains.Results All individuals generated a robust antibody response to BNT162b2 vaccination with all participants producing neutralizing antibodies following dose 2. IgM+ and IgG+ RBD-specific Bmem were generated after one vaccine dose, and those expressing IgG1 increased in absolute number after dose 2. The majority of RBD-specific Bmem bound the Gamma and/or Delta variants, and this proportion significantly increased after the second dose.Conclusion The second dose of BNT162b2 increases the number of circulating Ig-class switched RBD-specific Bmem. Importantly, the second dose of vaccination is required for a high frequency of RBD-specific Bmem to recognize Gamma and Delta variants. This suggests that dose 2 not only increases the number of RBD-specific Bmem but also the affinity of the Bmem to overcome the point mutations in VoC.Competing Interest StatementMCvZ, REOH and PMH are inventors on a patent application related to this work. SJB is an employee of and owns stock in BD. All the other authors declare no conflict of interest.