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J Gen Virol . The impact of pre-existing immunity on the emergence of within-host immune-escape mutations in Omicron lineages

tetano

Editor, Senior Moderator
J Gen Virol


. 2025 May;106(5):002108.
doi: 10.1099/jgv.0.002108. The impact of pre-existing immunity on the emergence of within-host immune-escape mutations in Omicron lineages

Muna N Ahmed[SUP] 1 [/SUP], Ummay Salma Abu Habib[SUP] 2 [/SUP], Abdallah M Abdallah[SUP] 3 [/SUP], Mohamed M Emara[SUP] 3 [/SUP], Arnab Pain[SUP] 4 [/SUP], Asmaa A Althani[SUP] 1 2 [/SUP], Gheyath K Nasrallah[SUP] 2 [/SUP], Hadi M Yassine[SUP] 1 2 [/SUP], Hebah A Al-Khatib[SUP] 1 [/SUP]



Affiliations
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.

Keywords: SARS-CoV-2; immune pressure; quasispecies; vaccination; virus evolution.

 
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