SARS-CoV-2 Infection or COVID-19 mRNA Vaccination Elicits Partially Different Spike-Reactive Memory B Cell Responses...

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• The COVID-19 pandemic offered a unique model to compare immune responses from natural infection versus vaccination against SARS-CoV-2.
• Understanding differences in B cell memory (Bmem) elicited by infection versus mRNA vaccination is crucial for evaluating vaccine efficacy and long-term immunity.

Purpose of the Study:

• To comprehensively analyze SARS-CoV-2 Spike (S-antigen)-reactive memory B cells (Bmem) following primary infection or mRNA vaccination in immunologically naive subjects.
• To test the hypothesis that the route of initial S-antigen encounter (lung mucosa during infection vs. intramuscular injection during vaccination) influences Bmem responses.

Main Methods:

• Analysis of cryopreserved peripheral blood mononuclear cells (PBMCs) from individuals post-primary SARS-CoV-2 infection (Wuhan-Hu-1 strain) or after an initial mRNA prime-boost regimen.
• ImmunoSpot® assays were employed to quantify S-antigen-reactive Bmem frequency, immunoglobulin (Ig) class/subclass usage, and cross-reactivity.
• Pre-pandemic blood samples served as naive controls.

Main Results:

• Spike-reactive Bmem repertoires post-infection and post-vaccination were largely similar, with prevalent induction of IgG1+ Bmem in both groups (~30% targeting the S-antigen Receptor Binding Domain).
• Cross-reactivity with the Omicron (BA.1) Receptor Binding Domain was comparable between infection and vaccination cohorts.
• Distinct differences included preferential induction of IgA+ Bmem after infection and detection of IgG4+ Bmem exclusively after vaccination.

Conclusions:

• SARS-CoV-2 infection and WH1-S encoding mRNA vaccination elicit subtly different Bmem responses in naive individuals.
• The immunological relevance of these observed differences concerning protective immunity requires further investigation.
• The ImmunoSpot® technique is demonstrated as a feasible method for comprehensive antigen-specific B cell memory monitoring in large cohorts.