# The impact of pre-existing immunity on the emergence of within-host immune-escape mutations in Omicron lineages

## TL;DR

This study explores how prior immunity affects mutations in Omicron variants of SARS-CoV-2 within infected individuals.

## Contribution

It identifies sub-consensus antigenic mutations in vaccinated individuals, suggesting vaccine-induced immune pressure.

## Key findings

- Vaccination status had limited impact on within-host diversity of Omicron variants.
- Sub-consensus antigenic mutations were more prevalent in vaccinated individuals.
- Four high-prevalence antigenic mutations were found absent in global GISAID data.

## Abstract

The Omicron variant of SARS-CoV-2 circulating amongst highly immunized populations is anticipated to induce immunological pressures, potentially compromising existing immunity. This study investigates vaccine-induced immunity’s impact on within-host diversity of Omicron variants and evaluates sub-consensus mutations at spike protein antigenic sites. Next-generation sequencing assessed the within-host diversity of 728 Omicron-positive samples (421 vaccinated; 307 unvaccinated). Quantitative analysis revealed limited vaccine impact, regardless of lineage, vaccine type or doses. Non-lineage mutations (39, 33 and 25 in BA.2*, BA.4* and BA.5* lineages, respectively) were detected, some showing higher incidence in vaccinated individuals. Six mutations detected at sub-consensus levels at antigenic sites suggest increased immune pressure on the spike protein in vaccinated individuals. Four high-prevalence antigenic mutations, absent from global GISAID sequences, were identified. Although within-host diversity did not significantly differ between vaccination statuses, detected mutations suggest that vaccine-induced immunity may influence within-host mutation patterns.