Quirk Grace E, Schoenle Marta V, Peyton Kameron L, Uhrlaub Jennifer L, Lau Branden, Burgess Jefferey L, Ellingson Katherine, Beitel Shawn, Romine James, Lutrick Karen, Fowlkes Ashley, Britton Amadea, Tyner Harmony L, Caban-Martinez Alberto J, Naleway Allison, Gaglani Manjusha, Yoon Sarang, Edwards Laura, Olsho Lauren, Dake Michael, LaFleur Bonnie J, Nikolich Janko Ž, Sprissler Ryan, Worobey Michael, Bhattacharya Deepta
Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ, USA.
Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA.
medRxiv. 2023 Sep 14:2023.09.12.23295384. doi: 10.1101/2023.09.12.23295384.
Vaccine-induced immunity may impact subsequent responses to drifted epitopes in SARS-CoV-2 variants, but this has been difficult to quantify due to the challenges in recruiting unvaccinated control groups whose first exposure to SARS-CoV-2 is a primary infection. Through local, statewide, and national SARS-CoV-2 testing programs, we were able to recruit cohorts of individuals who had recovered from either primary or post-vaccination infections by either the Delta or Omicron BA.1 variants. Regardless of variant, we observed greater Spike-specific and neutralizing antibody responses in post-vaccination infections than in those who were infected without prior vaccination. Through analysis of variant-specific memory B cells as markers of responses, we observed that Delta and Omicron BA.1 infections led to a marked shift in immunodominance in which some drifted epitopes elicited minimal responses, even in primary infections. Prior immunity through vaccination had a small negative impact on these responses, but this did not correlate with cross-reactive memory B cells, arguing against competitive inhibition of naïve B cells. We conclude that dampened B cell responses against drifted epitopes are mostly a function of altered immunodominance hierarchies that are apparent even in primary infections, with a more modest contribution from pre-existing immunity, perhaps due to accelerated antigen clearance.
疫苗诱导的免疫可能会影响后续对新冠病毒变异株中发生漂移的表位的反应，但由于招募未接种疫苗的对照组存在挑战，其首次接触新冠病毒是初次感染，因此难以对此进行量化。通过地方、州和全国性的新冠病毒检测项目，我们得以招募到从德尔塔或奥密克戎BA.1变异株引起的初次感染或疫苗接种后感染中康复的个体队列。无论变异株如何，我们观察到疫苗接种后感染的个体中，刺突蛋白特异性和中和抗体反应比未接种疫苗而感染的个体更强。通过分析作为反应标志物的变异株特异性记忆B细胞，我们观察到德尔塔和奥密克戎BA.1感染导致免疫优势发生显著转变，即一些发生漂移的表位引发的反应极小，即使在初次感染中也是如此。通过疫苗接种获得的既往免疫对这些反应有轻微负面影响，但这与交叉反应性记忆B细胞无关，这表明不存在对幼稚B细胞的竞争性抑制。我们得出结论，针对发生漂移的表位的B细胞反应减弱主要是免疫优势等级改变的结果，这种改变在初次感染中就很明显，既往免疫的影响相对较小，这可能是由于抗原清除加速所致。
