Division of Infectious Diseases, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
J Immunol. 2023 Apr 1;210(7):947-958. doi: 10.4049/jimmunol.2200920.
COVID-19 disproportionately affects persons with HIV (PWH) in worldwide locations with limited access to SARS-CoV-2 vaccines. PWH exhibit impaired immune responses to some, but not all, vaccines. Lymph node (LN) biopsies from PWH demonstrate abnormal LN structure, including dysregulated germinal center (GC) architecture. It is not clear whether LN dysregulation prevents PWH from mounting Ag-specific GC responses in the draining LN following vaccination. To address this issue, we longitudinally collected blood and draining LN fine needle aspiration samples before and after SARS-CoV-2 vaccination from a prospective, observational cohort of 11 PWH on antiretroviral therapy: 2 who received a two-dose mRNA vaccine series and 9 who received a single dose of the Ad26.COV2.S vaccine. Following vaccination, we observed spike-specific Abs, spike-specific B and T cells in the blood, and spike-specific GC B cell and T follicular helper cell responses in the LN of both mRNA vaccine recipients. We detected spike-specific Abs in the blood of all Ad26.COV2.S recipients, and one of six sampled Ad26.COV2.S recipients developed a detectable spike-specific GC B and T follicular helper cell response in the draining LN. Our data show that PWH can mount Ag-specific GC immune responses in the draining LN following SARS-CoV-2 vaccination. Due to the small and diverse nature of this cohort and the limited number of available controls, we are unable to elucidate all potential factors contributing to the infrequent vaccine-induced GC response observed in the Ad26.COV2.S recipients. Our preliminary findings suggest this is a necessary area of future research.
COVID-19 在全球范围内那些获得 SARS-CoV-2 疫苗有限的地方对艾滋病毒感染者（PWH）造成不成比例的影响。PWH 对某些疫苗表现出免疫反应受损，但并非所有疫苗。来自 PWH 的淋巴结（LN）活检显示异常 LN 结构，包括失调的生发中心（GC）结构。目前尚不清楚 LN 失调是否会阻止 PWH 在接种疫苗后在引流 LN 中产生针对抗原的特异性 GC 反应。为了解决这个问题，我们从接受抗逆转录病毒治疗的 11 名 PWH 的前瞻性观察队列中，在接种 SARS-CoV-2 疫苗前后纵向收集了血液和引流 LN 细针抽吸样本：2 名接受了两剂 mRNA 疫苗系列接种，9 名接受了一剂 Ad26.COV2.S 疫苗接种。接种疫苗后，我们在接受 mRNA 疫苗接种者的血液中观察到了刺突特异性 Abs、刺突特异性 B 和 T 细胞，以及 LN 中刺突特异性 GC B 细胞和滤泡辅助 T 细胞反应。我们在所有 Ad26.COV2.S 接受者的血液中检测到了刺突特异性 Abs，在 6 名接受 Ad26.COV2.S 接种者中，有 1 名在引流 LN 中发展出了可检测到的刺突特异性 GC B 和滤泡辅助 T 细胞反应。我们的数据表明，PWH 可以在接种 SARS-CoV-2 疫苗后在引流 LN 中产生针对抗原的特异性 GC 免疫反应。由于该队列的规模较小且多样化，以及可用对照的数量有限，我们无法阐明导致 Ad26.COV2.S 接受者中观察到的疫苗诱导 GC 反应不频繁的所有潜在因素。我们的初步发现表明，这是未来研究的一个必要领域。
