Since the emergence of SARS-CoV-2, humans have been exposed to distinct SARS-CoV-2 antigens, either by infection with different variants, and/or vaccination. Population immunity is thus highly heterogeneous, but the impact of such heterogeneity on the effectiveness and breadth of the antibody-mediated response is unclear. We measured antibody-mediated neutralisation responses against SARS-CoV-2Wuhan, SARS-CoV-2α, SARS-CoV-2δ and SARS-CoV-2ο pseudoviruses using sera from patients with distinct immunological histories, including naive, vaccinated, infected with SARS-CoV-2Wuhan, SARS-CoV-2α or SARS-CoV-2δ, and vaccinated/infected individuals. We show that the breadth and potency of the antibody-mediated response is influenced by the number, the variant, and the nature (infection or vaccination) of exposures, and that individuals with mixed immunity acquired by vaccination and natural exposure exhibit the broadest and most potent responses. Our results suggest that the interplay between host immunity and SARS-CoV-2 evolution will shape the antigenicity and subsequent transmission dynamics of SARS-CoV-2, with important implications for future vaccine design.

中文翻译：

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SARS-CoV-2 的进化和患者的免疫史决定了抗体介导免疫的广度和效力


自 SARS-CoV-2 出现以来，人类通过感染不同变体和/或接种疫苗而暴露于不同的 SARS-CoV-2 抗原。因此，群体免疫具有高度异质性，但这种异质性对抗体介导反应的有效性和广度的影响尚不清楚。我们使用来自具有不同免疫史的患者（包括初次接种疫苗的患者、感染过 SARS-CoV 的患者）的血清，测量了针对 SARS-CoV-2Wuhan、SARS-CoV-2α、SARS-CoV-2δ 和 SARS-CoV-2ο 假病毒的抗体介导的中和反应。 CoV-2Wuhan、SARS-CoV-2α 或 SARS-CoV-2δ 以及已接种疫苗/感染的个体。我们表明，抗体介导的反应的广度和效力受到暴露的数量、变异和性质（感染或疫苗接种）的影响，并且通过疫苗接种和自然暴露获得混合免疫力的个体表现出最广泛和最有力的回应。我们的结果表明，宿主免疫和 SARS-CoV-2 进化之间的相互作用将塑造 SARS-CoV-2 的抗原性和随后的传播动力学，对未来的疫苗设计具有重要意义。