#OA1-AM25-SN-02 - Effect of Immune Priming with Pre-Omicron SARS-Cov-2 Antigenic Stimuli on Antibody Responses Among Blood Donors with Omicron Infections and Reinfections

Background/Case Studies: The emergence of the SARS-CoV-2 omicron variant, characterized by enhanced transmissibility and immune evasion, challenged vaccine strategies based on the ancestral Wuhan-Hu-1 strain. Breakthrough infections in vaccinated individuals have raised concerns about the durability and adaptability of immune memory, particularly in light of immunological imprinting—where the immune system’s initial exposure to a specific SARS-CoV-2 variant shapes subsequent response. In this study, we examined the effect of immunological imprinting on humoral immunity in blood donors who experienced omicron infections or reinfections.

Study

Design/Methods:

We analyzed longitudinal antibody responses in 51 donors from the U.S. Nationwide Blood Donor Cohort Program (NBDC), grouped by prior immune exposure, identified using both survey and serology criteria from January 2021 to July 2023: 18 unvaccinated individuals with primary omicron infection, 20 individuals vaccinated with the ancestral strain vaccine, and 13 previously infected with pre-omicron variants (~5 timepoints per donor, total of 254). We used Meso Scale Discovery (MSD) assays for binding antibodies (V-PLEX SARS-CoV-2 Panel 37 Kit and Key Variant Spike Panel 1 Kit, including spike and nucleocapsid ancestral, alpha, beta, delta variants and 11 additional omicron variants) to assess antibody kinetics.

Results/Findings:

Our findings revealed that individuals primed by ancestral-strain-based vaccination developed the highest levels of spike-binding antibodies following omicron infection (mean 173,241 U/mL across all variants, 95% CI 30,236-190,654). Those with prior pre-omicron infection exhibited intermediate responses (26,821 AU/mL, 5,449-96,201), while unprimed individuals showed the lowest post-infection antibody levels (5,531 AU/mL, 3,996 – 21,942). Antibody levels increased following each immunological event in the 3 groups, but the magnitude was influenced by immune history (Fig.1). These results highlight the enduring influence of immunological imprinting on humoral immunity to evolving SARS-CoV-2 variants.

Conclusions:

This study investigated the pivotal role of immunological imprinting in shaping antibody responses to SARS-CoV-2, particularly after omicron infection or reinfection, while highlighting the essential role of blood donors in advancing biomedical research. Our data show that individuals primed by ancestral vaccination mount more robust antibody responses than those unvaccinated or primed by pre-omicron infection. These findings suggest that early antigenic exposure affects the magnitude, breadth and quality of subsequent immune responses, with important implications for booster vaccine strategies.