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叙利亚仓鼠中对 SARS-CoV-2 再感染的免疫持久性和保护作用。

Immune durability and protection against SARS-CoV-2 re-infection in Syrian hamsters.

机构信息

Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA, USA.

The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA, USA.

出版信息

Emerg Microbes Infect. 2022 Dec;11(1):1103-1114. doi: 10.1080/22221751.2022.2058419.

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a pandemic. As immunity to endemic human coronaviruses (i.e. NL63 or OC43) wanes leading to re-infection, it was unknown if SARS-CoV-2 immunity would also decline permitting repeat infections. Recent case reports confirm previously infected individuals can become re-infected; however, re-infection may be due to heterogeneity in the initial infection or the host immune response, or may be the result of infection with a variant strain that escapes pre-existing immunity. To control these variables, we utilized the Syrian hamster model to evaluate the duration of immunity and susceptibility to re-infection with SARS-CoV-2. Hamsters were given a primary mock or SARS-CoV-2 infection (culture media or 10 TCID50 USA/WA1/2020 isolate, respectively). Mock and SARS-CoV-2 infected hamsters were then given a secondary SARS-CoV-2 infection at 1, 2, 4, or 6 months post-primary infection ( = 14/time point/group). After the primary SARS-CoV-2 infection, hamsters developed anti-spike protein IgG, IgA, and neutralizing antibodies, and these antibodies were maintained for at least 6 months. Upon secondary SARS-CoV-2 challenge, previously SARS-CoV-2 infected animals were protected from weight loss, while all previously mock-infected animals became infected and lost weight. Importantly, despite having high titres of antibodies, one SARS-CoV-2 infected animal re-challenged at 4 months had a breakthrough infection with replicating virus in the upper and lower respiratory tract. These studies demonstrate immunity to SARS-CoV-2 is maintained for 6 months; however, protection may be incomplete and, even in the presence of high antibody titres, previously infected hosts may become re-infected.

摘要

严重急性呼吸综合征冠状病毒 2 型(SARS-CoV-2)已造成大流行。由于内源性人类冠状病毒(即 NL63 或 OC43)的免疫逐渐减弱导致再次感染,因此尚不清楚 SARS-CoV-2 免疫是否也会下降从而允许重复感染。最近的病例报告证实,先前感染过的个体可能会再次感染;然而,再次感染可能是由于初始感染的异质性或宿主免疫反应,也可能是感染了逃避现有免疫的变异株的结果。为了控制这些变量,我们利用叙利亚仓鼠模型来评估 SARS-CoV-2 感染后的免疫持续时间和再次感染的易感性。仓鼠接受初次模拟或 SARS-CoV-2 感染(分别为培养基或 10 TCID50 USA/WA1/2020 分离株)。然后,在初次感染后 1、2、4 或 6 个月(每组 = 14 个时间点/组),对模拟和 SARS-CoV-2 感染的仓鼠进行二次 SARS-CoV-2 感染。在初次 SARS-CoV-2 感染后,仓鼠产生了针对刺突蛋白的 IgG、IgA 和中和抗体,这些抗体至少维持了 6 个月。在二次 SARS-CoV-2 攻击时,先前感染过 SARS-CoV-2 的动物免受体重减轻的影响,而所有先前感染过模拟病毒的动物都被感染并减轻了体重。重要的是,尽管有高滴度的抗体,在 4 个月时再次接受 SARS-CoV-2 挑战的一只动物仍发生了突破性感染,在上呼吸道和下呼吸道中复制了病毒。这些研究表明,对 SARS-CoV-2 的免疫力可维持 6 个月;然而,保护可能不完全,即使存在高抗体滴度,先前感染的宿主也可能再次感染。

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