Dearlove Bethany L, Fries Anthony C, Epsi Nusrat J, Richard Stephanie A, Ganesan Anuradha, Huprikar Nikhil, Lindholm David A, Mende Katrin, Colombo Rhonda E, Colombo Christopher, Bai Hongjun, Larson Derek T, Ewers Evan C, Lalani Tahaniyat, Smith Alfred G, Berjohn Catherine M, Maves Ryan C, Jones Milissa U, Saunders David, Maldonado Carlos J, Mody Rupal M, Bazan Samantha E, Tribble David R, Burgess Timothy, Simons Mark P, Agan Brian K, Pollett Simon D, Rolland Morgane
US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, United States.
Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Bethesda, MD 20817, United States.
Virus Evol. 2024 Sep 2;10(1):veae071. doi: 10.1093/ve/veae071. eCollection 2024.
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.
2019冠状病毒病（COVID-19）疫苗突破性感染在所有流行的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变异株流行期间都很重要，但疫苗特异性SARS-CoV-2病毒多样化对疫苗失效的影响仍不清楚。本研究分析了2020年12月至2022年4月期间从军事卫生系统受益人中收集的595个SARS-CoV-2序列，以调查疫苗接种对病毒多样性的影响。通过根据参与者的疫苗接种状况比较序列，我们发现有限的证据表明疫苗接种与SARS-CoV-2刺突蛋白中病毒多样性增加有关，并且我们几乎没有发现主要变异株内存在实质性筛选效应的证据；相反，我们表明快速的变异株替代限制了基因型内COVID-19疫苗株的免疫逃逸。这些数据表明，在过去以及可能在未来SARS-CoV-2变异株快速替代的时期，由于在短时间内发生的大规模感染和疫苗接种，疫苗介导的效应与病毒多样性的其他驱动因素混在了一起。然而，我们的结果也凸显了在非安慰剂对照临床试验之外使用筛选分析方法的一些局限性。
