PT - JOURNAL ARTICLE AU - Kim, Sang Il AU - Noh, Jinsung AU - Kim, Sujeong AU - Choi, Younggeun AU - Yoo, Duck Kyun AU - Lee, Yonghee AU - Lee, Hyunho AU - Jung, Jongtak AU - Kang, Chang Kyung AU - Song, Kyoung-Ho AU - Choe, Pyoeng Gyun AU - Kim, Hong Bin AU - Kim, Eu Suk AU - Kim, Nam-Joong AU - Seong, Moon-Woo AU - Park, Wan Beom AU - Oh, Myoung-don AU - Kwon, Sunghoon AU - Chung, Junho TI - Stereotypic neutralizing V<sub>H</sub> antibodies against SARS-CoV-2 spike protein receptor binding domain in patients with COVID-19 and healthy individuals AID - 10.1126/scitranslmed.abd6990 DP - 2021 Jan 27 TA - Science Translational Medicine PG - eabd6990 VI - 13 IP - 578 4099 - http://stm.sciencemag.org/content/13/578/eabd6990.short 4100 - http://stm.sciencemag.org/content/13/578/eabd6990.full AB - Stereotypic antibodies (Abs) are produced in healthy individuals by preexisting naïve B cells that have not undergone somatic hypermutation or class switching. Kim et al. have identified stereotypic neutralizing Abs (nAbs) against SARS-CoV-2 spike protein receptor binding domain (RBD) in healthy individuals and patients with COVID-19. They detected RBD-specific stereotypic variable heavy chain (VH) Ab clonotypes composed of Ig heavy variable 3-53 (IGHV3-53) or IGHV3-66 and Ig heavy joining 6 (IGHJ6) genes in 13 of 17 patients with COVID-19. One stereotypic nAb could inhibit in vitro replication of a clinical isolate of SARS-CoV-2. These VH clonotypes were also found in 6 of 10 healthy individuals with no evidence of exposure to SARS-CoV-2, and together, these findings provide evidence of the presence of preexisting nAbs to SARS-CoV-2.Stereotypic antibody clonotypes exist in healthy individuals and may provide protective immunity against viral infections by neutralization. We observed that 13 of 17 patients with COVID-19 had stereotypic variable heavy chain (VH) antibody clonotypes directed against the receptor binding domain (RBD) of SARS-CoV-2 spike protein. These antibody clonotypes were composed of immunoglobulin heavy variable 3-53 (IGHV3-53) or IGHV3-66 and immunoglobulin heavy joining 6 (IGHJ6) genes. These clonotypes included IgM, IgG3, IgG1, IgA1, IgG2, and IgA2 subtypes and had minimal somatic mutations, which suggested swift class switching after SARS-CoV-2 infection. The different IGHV chains were paired with diverse light chains resulting in binding to the RBD of SARS-CoV-2 spike protein. Human antibodies specific for the RBD can neutralize SARS-CoV-2 by inhibiting entry into host cells. We observed that one of these stereotypic neutralizing antibodies could inhibit viral replication in vitro using a clinical isolate of SARS-CoV-2. We also found that these VH clonotypes existed in 6 of 10 healthy individuals, with IgM isotypes predominating. These findings suggest that stereotypic clonotypes can develop de novo from naïve B cells and not from memory B cells established from prior exposure to similar viruses. The expeditious and stereotypic expansion of these clonotypes may have occurred in patients infected with SARS-CoV-2 because they were already present.