Memory B cell responses to Omicron subvariants after SARS-CoV-2 mRNA breakthrough infection in humans

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• A third mRNA vaccine dose enhances protection against severe COVID-19.
• The impact of breakthrough infections on immune memory responses remains understudied.

Purpose of the Study:

• To investigate the impact of breakthrough infections on memory antibody responses after a third or fourth antigenic exposure.
• To compare the effects of Delta and Omicron BA.1 infections on B cell memory.

Main Methods:

• Analysis of memory B cell responses following third (Delta) and fourth (Omicron BA.1) antigenic exposures.
• Assessment of antibody potency and breadth.

Main Results:

• A third antigenic exposure via Delta breakthrough infection increased memory B cells with antibody potency and breadth comparable to a third mRNA vaccine dose.
• A fourth antigenic exposure via Omicron BA.1 infection boosted variant-specific antibodies and memory B cells but did not enhance overall memory cell frequency, potency, or breadth.
• The fourth exposure's effects were limited to increased Omicron BA.1-specific memory.

Conclusions:

• A third antigenic exposure, particularly by Delta infection, elicits strain-specific memory responses and broadens the potency of memory B cells.
• A fourth antigenic exposure with Omicron BA.1 infection primarily increases strain-specific memory with minimal impact on the overall potency or breadth of memory B cell antibodies.
• Strain-specific boosting may have limited effects on the broader memory B cell compartment.