Immunity against conserved epitopes dominates after two consecutive exposures to SARS-CoV-2 Omicron BA.1

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) evolution presents challenges for vaccine efficacy.
• Previous exposure to wild-type SARS-CoV-2 can influence immune responses to variants like Omicron.
• Immune imprinting by initial exposures may affect subsequent adaptive immunity.

Purpose of the Study:

• To investigate the impact of immune imprinting on memory B cell responses after sequential exposures to wild-type and Omicron BA.1 SARS-CoV-2.
• To determine if prior imprinting limits the development of strain-specific immunity against Omicron variants.

Main Methods:

• Analysis of memory B cell populations in individuals with specific vaccination and infection histories.
• Assessment of antibody neutralization capacity against Omicron variants.
• Depletion of antibodies targeting conserved epitopes using wild-type spike protein bait.

Main Results:

• Individuals vaccinated with wild-type mRNA vaccines and subsequently infected/vaccinated with Omicron BA.1 showed a recall response dominated by memory B cells targeting conserved epitopes.
• Depleting antibodies recognizing conserved epitopes significantly reduced Omicron BA.1 neutralization.
• Spike-specific memory B cells recognizing conserved epitopes were more prevalent than Omicron BA.1-specific memory B cells.

Conclusions:

• Immune imprinting from initial SARS-CoV-2 exposures, including wild-type vaccines, can persistently limit the induction of strain-specific immune responses, even after multiple Omicron exposures.
• Vaccine adaptation strategies must account for pre-existing immune imprinting from prior infections and vaccinations to enhance protection against evolving viral variants.