Sang Il Kim, Jinsung Noh, Sujeong Kim, Younggeun Choi, Duck Kyun Yoo, Yonghee Lee, Hyunho Lee, Jongtak Jung, C. K. Kang, K. Song, P. G. Choe, Hong-Bin Kim, E. S. Kim, N. Kim, M. Seong, W. Park, M. Oh, Sunghoon Kwon, Junho Chung
Science Translational Medicine, 2021
Stereotypic neutralizing antibody clonotypes specific for SARS-CoV-2 receptor binding domain in patients with COVID-19 and healthy individuals. Neutralizing antibodies on hand 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.
Cited by 12 publications.
Field of study: Medicine