Abby Odle, Meenakshi Kar, Abhishek K Verma, Alan Sariol, David K Meyerholz, Mehul S Suthar, Lok-Yin Roy Wong, Stanley Perlman
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引用次数: 0
摘要
广泛的疫苗接种和自然感染已使随后感染或再次感染 SARS-CoV-2 后的严重疾病、住院和死亡率大大降低。新的疫苗配方是以流行的病毒株为基础的,这些病毒株在进化过程中更容易在人与人之间传播,也更容易逃避中和抗体反应。这种方法的一个假设是病毒的祖先毒株不会再次出现。对于以前没有通过接种疫苗或感染接触过祖先尖峰蛋白的人来说,这些毒株的复发可能是一个问题。为了解决这个问题,我们用最近的 SARS-CoV-2 变异株感染小鼠,然后用与祖先武汉-1 株(SARS2-N501YMA30)密切相关的高致病性小鼠适配病毒对小鼠进行挑战。我们发现,受挑战的小鼠虽然在再次感染时对 SARS2-N501YMA30 的中和抗体反应普遍较低或没有反应,但仍能免于死亡和体重大幅下降。先前感染过的小鼠的 T 细胞耗竭并没有减轻感染和临床疾病,但确实导致了鼻甲和某些肺部病毒清除动力学的延迟。与以前未接触过 SARS-CoV-2 的小鼠相比,以前感染过 SARS-CoV-2 的小鼠鼻甲中的组织常驻记忆 T 细胞水平明显升高。然而,在肺组织中却看不到这种表型。总之,这些结果表明,对新的循环变异体的免疫反应至少在一定程度上保护了小鼠免受祖先病毒的再次感染。
Tissue resident memory T cells contribute to protectionagainst heterologousSARS-CoV-2 challenge.
Widespread vaccination and natural infection have resulted in greatly decreased rates of severe disease, hospitalization and death after subsequent infection or reinfection with SARS-CoV-2. New vaccine formulations are based on circulating strains of virus, which have tended to evolve to more readily transmit human to human and to evade the neutralizing antibody response. An assumption of this approach is that ancestral strains of virus will not recur. Recurrence of these strains could be a problem for individuals not previously exposed to ancestral spike protein by vaccination or infection. Here, we addressed this question by infecting mice with recent SARS-CoV-2 variants and then challenging them with a highly pathogenic mouse-adapted virus closely related to the ancestral Wuhan-1 strain (SARS2-N501YMA30). We found that challenged mice were protected from death and substantial weight loss, even though they generally had low or no neutralizing antibody response to SARS2-N501YMA30 at the time of reinfection. T cell depletion from the previously infected mice did not diminish infection against clinical disease, although it did result in delayed kinetics of virus clearance in the nasal turbinate and in some cases, in the lungs. Levels of tissue resident memory T cells were significantly elevated in the nasal turbinate of previously infected mice compared to mice that had no previous exposure to SARS-CoV-2. However, this phenotype was not seen in lung tissues. Together, these results indicate that the immune response to newly circulating variants afforded protection against re-infection with the ancestral virus that was at least in part T cell based.
期刊介绍:
JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.