SARS-CoV-2 Neutralization Breadth Is Shaped by Variant Exposure and Immune History

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Emerging SARS-CoV-2 variants continually challenge vaccine-induced immunity.
• Understanding how prior exposure history impacts neutralizing responses is crucial for public health.

Purpose of the Study:

• To investigate the influence of distinct SARS-CoV-2 exposure histories on neutralizing antibody breadth against various viral variants.
• To assess the impact of infection, vaccination, and combined exposures on immune responses.

Main Methods:

• Plasma from 46 participants with defined SARS-CoV-2 exposure profiles was analyzed.
• Neutralizing breadth was evaluated against a panel of SARS-CoV-2 variants of concern and Omicron subvariants using pseudoparticles.

Main Results:

• Infection induced potent homologous but variable heterologous neutralization; vaccination alone yielded lower, more consistent responses.
• Repeated exposures (vaccination or breakthrough infection) significantly enhanced cross-variant neutralization.
• Highest neutralizing potency and breadth were seen with cumulative exposures, yet activity against recent Omicron subvariants (EG.5, HV.1, JN.1) remained limited.

Conclusions:

• Both the type and number of antigenic exposures significantly shape SARS-CoV-2 neutralizing responses.
• Cumulative exposures improve cross-variant immunity, but viral evolution necessitates ongoing surveillance and vaccine updates.