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This study analyzed 595 SARS-CoV-2 sequences collected from the Military Health System beneficiaries between December 2020 and April 2022 to investigate the impact of vaccination on viral diversity. By comparing sequences based on the vaccination status of the participant, we found limited evidence indicating that vaccination was associated with increased viral diversity in the SARS-CoV-2 spike, and we show little to no evidence of a substantial sieve effect within major variants; rather, we show that rapid variant replacement constrained intragenotype COVID-19 vaccine strain immune escape. These data suggest that, during past and perhaps future periods of rapid SARS-CoV-2 variant replacement, vaccine-mediated effects were subsumed with other drivers of viral diversity due to the massive scale of infections and vaccinations that occurred in a short time frame. However, our results also highlight some limitations of using sieve analysis methods outside of placebo-controlled clinical trials.<\/jats:p>","DOI":"10.1093\/ve\/veae071","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T12:35:09Z","timestamp":1725280509000},"source":"Crossref","is-referenced-by-count":1,"title":["SARS-CoV-2 variant replacement constrains vaccine-specific viral diversification"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3653-4592","authenticated-orcid":false,"given":"Bethany L","family":"Dearlove","sequence":"first","affiliation":[{"name":"US Military HIV Research Program, Walter Reed Army Institute of Research , 503 Robert Grant Avenue, Silver Spring, MD 20910,","place":["United States"]},{"name":"Henry M Jackson Foundation for the Advancement of Military Medicine, Inc. , 6720A Rockledge Drive, Bethesda, MD 20817,","place":["United 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