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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

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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

    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 1 , Ummay Salma Abu Habib 2 , Abdallah M Abdallah 3 , Mohamed M Emara 3 , Arnab Pain 4 , Asmaa A Althani 1 2 , Gheyath K Nasrallah 2 , Hadi M Yassine 1 2 , Hebah A Al-Khatib 1



    AffiliationsAbstract

    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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