2338. Robust and Persistent B Cell Responses Following Third Dose SARS-CoV-2 Vaccine Determine Protection from COVID-19

BACKGROUND: The immunological memory to SARS-CoV-2 (SCV-2) vaccination has multiple components, with robust antibody (Ab) and B cell responses demonstrated post vaccination. The extent and persistence of T cell responses to vaccination remains unclear. We explored SCV-2 specific Ab, B cell and T cell responses to 3(rd) dose vaccine and their relationship to incident COVID-19. METHODS: In plasma from adults enrolled in a multicentre prospective cohort, sampled before, 14 days and 10 months post 3(rd) dose vaccine (BNT162b2) we measured anti-SCV-2 receptor binding domain (RBD) Ab by electrochemiluminescence assays. Subjects reported incident COVID-19 that occurred post vaccination. In a subanalysis, we assessed SCV-2-specific plasma cell, memory B cell and T cell responses in peripheral blood mononuclear cells after stimulation with wild type (WT) RBD, WT full Spike antigen, Omicron RBD and Omicron S1 antigens by ELISpot (Mabtech ELISpot, Sweden, Fig 1). We compared between-group differences in immunological outcomes by incident infection by Wilcoxon signed rank or Mann–Whitney U tests. Data are median (IQR) unless specified. [Figure: see text] RESULTS: Of 132 subjects (age 43 [32-50], 81% female (Table 1), 47 (36%) reported incident SCV-2 infection at 18 (16-21) weeks post 3(rd) vaccine. 76 subjects contributed to the cellular immunity subanalysis [23 of whom provided additional samples 10 months post vaccine (Table 1)]. RBD titres and B cell responses increased significantly 2 weeks post 3(rd) vaccine (Fig 2, p< 0.001), with RBD titres and WT-specific memory B cell responses remaining significantly higher than pre-booster vaccine levels at 10 months (Fig 2, p< 0.001). In contrast, there was no significant difference in T cell responses at two weeks or 10 months post 3(rd) dose vaccine (Fig 2). There was no difference in 2-week post vaccine RBD or T cell responses in those with and without incident SCV-2 infection. However, those with incident infection had significantly lower WT RBD-specific plasma and memory B cell levels (Table 2, all p< 0.05). [Figure: see text] [Figure: see text] [Figure: see text] CONCLUSION: 3(rd) dose vaccination induced robust antibody and B cell responses which persist at 10 months, but not T cell responses. Higher memory B cell responses post vaccination, rather than circulating antibody titres or T cells, are associated with protection from subsequent infection. DISCLOSURES: Oliver A. Cornely, MD PhD, DZIF: Advisor/Consultant|DZIF: Board Member|DZIF: Grant/Research Support|DZIF: Honoraria|DZIF: Stocks/Bonds