Immune recall improves antibody durability and breadth to SARS-CoV-2 variants

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Immune memory is characterized by enhanced antibody responses upon re-exposure to pathogens.
• Viral evolution necessitates understanding the breadth and longevity of antibody memory against emerging variants.
• Assessing immune recall's impact on secreted antibody responses is vital for predicting long-term protection.

Purpose of the Study:

• To analyze severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variant recognition and antibody dynamics after infection, vaccination, and boosting.
• To investigate the influence of antigen challenge history on antibody memory repertoire composition and longevity.

Main Methods:

• Analysis of SARS-CoV-2 variant recognition.
• Monitoring of memory B cell dynamics.
• Quantification of secreted antibodies over time post-infection, vaccination, and boosting.
• Assessment of neutralization potency and antibody stability across different SARS-CoV-2 variants.

Main Results:

• A two-dose SARS-CoV-2 vaccination after natural infection yielded superior longitudinal antibody stability and broad recognition of Beta, Gamma, Delta, and Omicron variants.
• A third messenger RNA vaccine dose in COVID-naïve individuals provided cross-variant neutralization evenness and stability comparable to hybrid immunity.
• Unvaccinated individuals with faster COVID-19 recovery and higher cross-reactive memory B cells to endemic coronaviruses showed enhanced antibody stability.

Conclusions:

• SARS-CoV-2 antigen exposure history shapes the speed, magnitude, and cross-variant breadth of antibody responses.
• Memory B cell cross-reactivity to conserved viral regions, like the S2 spike region, contributes to enhanced antibody stability and affinity.
• Understanding these dynamics is crucial for developing effective vaccines and predicting long-term immunity against SARS-CoV-2 and its variants.