Prior Vaccination Exceeds Prior Infection in Eliciting Innate and Humoral Immune Responses in Omicron Infected...

Area of Science:

• Immunology
• Virology
• Genomics

Background:

• Omicron variant infections elicit a less robust antibody response compared to other SARS-CoV-2 variants.
• Understanding how prior vaccination and infection history influences immune responses to Omicron is crucial.

Purpose of the Study:

• To investigate the impact of prior vaccination and/or infection on disease severity, antibody responses, and immune transcriptomes following Omicron infection.
• To compare the immune response in different patient groups: unvaccinated/no prior infection, vaccinated/no prior infection, unvaccinated/prior infection, and vaccinated/prior infection.

Main Methods:

• Characterized disease severity, anti-Omicron spike antibody levels, and neutralizing activity in 83 Omicron-infected outpatients across four groups.
• Analyzed early transcriptomic responses following Omicron infection in outpatients and compared them to unvaccinated hospitalized patients with Alpha infection.
• Examined specific gene classes (OAS, IFIT, IFI27) involved in antiviral responses and disease outcome prediction.

Main Results:

• The vaccinated/no prior infection group exhibited the highest percentage of asymptomatic or mild disease (87%), while the unvaccinated/no prior infection group had the lowest (47%).
• Significant anti-Omicron spike antibody levels and neutralizing activity were detected in vaccinated individuals post-infection, unlike in the unvaccinated/no prior infection group.
• Vaccinated patients displayed a blunted interferon response, indicated by reduced expression of antiviral genes (OAS, IFIT, IFI27), compared to unvaccinated Omicron or Alpha infected patients.

Conclusions:

• Prior vaccination and/or infection significantly modulate the immune response to Omicron, leading to improved antibody levels and reduced disease severity.
• Vaccination status is a key determinant of robust antibody production and a milder clinical course following Omicron infection.
• The blunted interferon response in vaccinated individuals suggests a distinct immune modulation pathway that warrants further investigation.