An IGHG1 Variant Introgressed From Vindija Neanderthal Archaic Hominin Confers Enhanced Antibody Immunity Against SARS-CoV-2

How genetic polymorphisms of adaptive immune receptors influence population susceptibility to infectious diseases remains unclear. Here we describe the prevalence and provenance of a coding variant in IgG1 (G396R) that influences the IgG1 antibody response against SARS-CoV-2. G396R variant is negatively associated with susceptibility to COVID-19. The protective effect of the G396R variant is achieved by promoting the activation of memory B cells. G396R variant is highly polarized prevalence of the in Asian populations. LD analyses distinguished a 190kb LD block with the G396R variant closest to the peak, suggesting that the variant potentially have driven the selection. We investigated its origin and found the presence of the G396R variant in the Vindija Neanderthal. PCA analysis demonstrated the significant signals of Vindija Neanderthal introgression at the LD blocked G396R variant region. Conclusively, these results indicate that an introgressed Vindija Neanderthal IGHG1 variant confers enhanced antibody immunity against SARS-CoV-2.Funding Information: This study has been supported by Tsinghua University Spring Breeze Fund, Center for Life Sciences, and Institute for Immunology at Tsinghua University. This work is supported by grants from Ministry of Science and Technology of China Grants (2021YFC2300503 and 2021YFC2302403), National Natural Science Foundation of China (32141004, 81825010, 81730043, 81621002 to W. Liu, 81930061 to G. Deng) and Chongqing Natural Science Foundation (cstc2019jcyj-zdxmX0004).Conflict of Interests: The authors declared no financial or commercial conflicts of interest.Ethical Approval: Clinical sample processing and sequencing were respectively approved by Shenzhen Third People’s Hospital Ethics Committee and Wuhan Union Hospital Ethics Committee. This study was also approved by the Ethics Committee for Biomedical Studies at Tsinghua University.