1959. Lower B-Cell Responses Rather Than Circulating Antibody Titres Are Associated With SARS-CoV-2 Infection Post Third Dose COVID-19 Vaccination

• Published in: Open forum infectious diseases Vol. 9; no. Supplement_2
• Main Authors: Byrne, Joanne, Gu, Lili, Negi, Riya, Garcia-Leon, Alejandro, Alalwan, Dana, Gaillard, Colette Marie, Saini, Gurvin, Leamy, Kelly, Reynolds, Bearach, O’Gorman, Tessa, Kenny, Grace, O’Broin, Cathal, Feeney, Eoin R, Yousif, Obada, Cotter, Aoife, de Barra, Eoghan, Horgan, Mary, Landay, Alan, Doran, Peter, Gautier, Virginie, Mallon, Patrick
• Format: Journal Article
• Language: English
• Published: 15-12-2022
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofac492.1585

Abstract
Background
Which components of the immune response to SARS-CoV-2 vaccination best protect against subsequent infection remains unclear. We explored SARS-CoV-2 specific antibody and B-cell responses post 3rd dose vaccine and their relationship to subsequent SARS-CoV-2 infection.
Methods
In a multicentre prospective cohort, adult subjects provided samples before and 14 days (d14) post 3rd dose vaccine with Pfizer-BioNTech 162b2. At 18-22 weeks post vaccine, subjects self-reported SARS-CoV-2 infection (confirmed by PCR or antigen test). We used electrochemiluminescence assays to quantify antibodies to SARS-CoV-2 spike subunit 1 (S1), subunit 2 (S2) and receptor-binding domain (RBD) in plasma (reported in WHO IU/mL). In a subset of subjects, we assessed SARS-CoV-2 specific differentiated B-cell (plasma cell) and memory B-cell responses from peripheral blood mononuclear cells. Unstimulated plasma cells, and memory B cells stimulated with R848 and IL2, were seeded on plates coated with RBD or full Spike antigen and antigen-specific responses measured by ELISpot (Mabtech ELISpot, Sweden). We compared between group differences by Wilcoxon signed rank or Mann–Whitney tests. Data are median [IQR] unless specified.
Results
Of 133 subjects (age 43 [32-50], 81.2% female (table 1), 77 subjects in the B-cell subgroup (table 2)), 47 (35.3%) reported SARS-CoV-2 infection post 3rd vaccine. Antibody titres, plasma cell and memory B-cell responses all increased significantly at d14 post 3rd vaccine (Table 1 & 2, all P< 0.001). Although d14 antibody titres did not differ in those with and without subsequent infection (table 1), those reporting subsequent infection had significantly lower d14 RBD-specific plasma cells and a lower proportion of RBD-specific memory B-cells (Figure 1a-b, both P< 0.05). Similar results were observed with full-spike-specific memory B-cell responses (Figure 1d). The differences persisted when the non-infected group was restricted only to those reporting a confirmed close contact (n=26).
Conclusion
Infection following 3rd dose vaccine is associated with lower d14 circulating and memory B cell responses, but not antibody titres, suggesting B-cell responses better predict protection against subsequent SARS-CoV-2 infection.
Disclosures
All Authors: No reported disclosures.