Vaccination Shapes Within-Host SARS-CoV-2 Diversity of Omicron BA.2.2 Breakthrough Infection

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Low-frequency intrahost single-nucleotide variants (SNVs) in SARS-CoV-2 predict selection.
• The effect of vaccination on SARS-CoV-2 intrahost evolution is not well understood.

Purpose of the Study:

• Investigate the impact of vaccination status on SARS-CoV-2 intrahost genetic variation during the Omicron BA.2.2 wave.
• Determine if vaccination influences viral evolution and selection pressures.

Main Methods:

• Analyzed SARS-CoV-2 genetic variation in unvaccinated, partially vaccinated, and fully vaccinated individuals.
• Used pseudovirus neutralization assays and human leukocyte antigen (HLA) T-cell epitope cross-verification to assess immune-mediated selection.

Main Results:

• Fully vaccinated individuals exhibited reduced intrahost variant diversity compared to unvaccinated or partially vaccinated groups.
• Mutations were enriched in the spike protein gene in fully vaccinated individuals.
• No significant positive selection was observed in immunocompetent individuals, unlike in two immunocompromised cases with prolonged shedding.

Conclusions:

• Vaccine-induced immunity in SARS-CoV-2 infections is linked to decreased intrahost variant diversity and milder disease.
• Spike protein mutation enrichment indicates vaccine-induced selection pressure on SARS-CoV-2 evolution.