SARS-CoV-2 variant replacement constrains vaccine-specific viral diversification.

Coronavirus disease 2019 (COVID-19) vaccine breakthrough infections have been important for all circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant periods, but the contribution of vaccine-specific SARS-CoV-2 viral diversification to vaccine failure remains unclear. 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.
Competing Interests: The views expressed are those of the authors and do not reflect the official policy of the Uniformed Services University of the Health Sciences (USUHS), Department of the Army, Department of the Navy, the Department of the Air Force, the Department of Defense or the US Government, and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). The investigators have adhered to the policies for protection of human subjects as prescribed in 45 CFR 46. Drs Berjohn, Fries, Smith, Mody, Huprikar, Lindholm, Jones, Larson, Ewers; Ms Bazan; and Drs Saunders, Maldonado, Simons, Tribble, and Burgess are service members or employees of the US Government. This work was prepared as part of their official duties. Title 17 USC §105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 USC §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person’s official duties.
(© The Author(s) 2024. Published by Oxford University Press.)