Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination.
Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination.
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DOI：
10.1038/s41586-022-04865-0
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发表时间：
2022-07
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
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作者：
SARS-CoV-2 Delta和Omicron是全球关注的相关变体。虽然感染Delta的个体有发生严重肺部疾病的风险，但Omicron感染通常会导致较轻的症状，特别是在接种疫苗的个体中。问题是，广泛的Omicron感染是否会导致未来的交叉变异保护，加速大流行的结束。在这里，我们表明，没有接种疫苗，感染Omicron诱导小鼠和人类有限的体液免疫反应。来自过表达人ACE 2受体并感染Omicron的小鼠的血清仅中和Omicron，但不中和其他相关变体，而在WA 1和Delta感染后观察到更广泛的交叉变体中和。与WA 1和Delta不同，Omicron在感染动物的肺部和大脑中复制至低水平，导致轻微疾病，促炎细胞因子表达减少，肺部驻留T细胞的激活减少。来自未接种疫苗并感染Omicron的个体的血清显示仅Omicron本身的相同有限中和。相比之下，Omicron突破感染诱导针对所有相关变体的总体较高中和滴度。我们的研究结果表明，Omicron感染增强了预先存在的疫苗引起的免疫力，但就其本身而言，可能不会对未接种疫苗的个体提供广泛的保护。接种疫苗后感染Omicron会产生针对其他相关变体的交叉中和抗体，而这会在未接种疫苗的个体中诱导对非Omicron变体的有限反应。
SARS-CoV-2 Delta and Omicron are globally relevant variants of concern. Although individuals infected with Delta are at risk of developing severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals. The question arises of whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic. Here we show that without vaccination, infection with Omicron induces a limited humoral immune response in mice and humans. Sera from mice overexpressing the human ACE2 receptor and infected with Omicron neutralize only Omicron, but not other variants of concern, whereas broader cross-variant neutralization was observed after WA1 and Delta infections. Unlike WA1 and Delta, Omicron replicates to low levels in the lungs and brains of infected animals, leading to mild disease with reduced expression of pro-inflammatory cytokines and diminished activation of lung-resident T cells. Sera from individuals who were unvaccinated and infected with Omicron show the same limited neutralization of only Omicron itself. By contrast, Omicron breakthrough infections induce overall higher neutralization titres against all variants of concern. Our results demonstrate that Omicron infection enhances pre-existing immunity elicited by vaccines but, on its own, may not confer broad protection against non-Omicron variants in unvaccinated individuals. Infection with Omicron after vaccination produces cross-neutralizing antibodies to other variants of concern, whereas this induces a limited response to non-Omicron variants in unvaccinated individuals.