Abstract:
Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T cell immune memory is critical for continued protection against severe COVID-19. We examined T cell responses to SARS-CoV-2 approximately 1.5 years since Omicron first emerged. We describe sustained CD4+ and CD8+ spike-specific T cell memory responses in healthcare workers in South Africa (n = 39) who were vaccinated and experienced at least one SARS-CoV-2 infection. Spike-specific T cells are highly cross-reactive with all Omicron variants tested, including BA.2.86. Abundant nucleocapsid and membrane-specific T cells are detectable in most participants. The bulk of SARS-CoV-2-specific T cell responses have an early-differentiated phenotype, explaining their persistent nature. Overall, hybrid immunity leads to the accumulation of spike and non-spike T cells evident 3.5 years after the start of the pandemic, with preserved recognition of highly mutated SARS-CoV-2 variants.
摘要:
正在进行的严重急性呼吸道综合症冠状病毒2(SARS-CoV-2)的进化已经产生了在全球占主导地位的重组Omicron谱系(XBB.1),以及超突变变体的出现(BA.2.86)。在这种情况下,持久和交叉反应性T细胞免疫记忆对于持续预防严重COVID-19至关重要。我们检查了自Omicron首次出现以来大约1.5年的T细胞对SARS-CoV-2的反应。我们描述了南非(n=39)的医护人员中持续的CD4和CD8尖峰特异性T细胞记忆反应,他们接种了疫苗并经历了至少一次SARS-CoV-2感染。Spike特异性T细胞与所有测试的Omicron变体具有高度交叉反应性,包括BA.2.86。在大多数参与者中可以检测到丰富的核衣壳和膜特异性T细胞。大部分SARS-CoV-2特异性T细胞反应具有早期分化表型,解释他们的坚持性质。总的来说,混合免疫导致在大流行开始3.5年后明显的尖峰和非尖峰T细胞的积累,保留对高度突变的SARS-CoV-2变体的识别。