Convergent structural features of respiratory syncytial virus neutralizing antibodies and plasticity of the site V epitope on prefusion F

• Published in: PLoS pathogens Vol. 16; no. 11; p. e1008943
• Main Authors: Harshbarger, Wayne, Tian, Sai, Wahome, Newton, Balsaraf, Ankita, Bhattacharya, Deep, Jiang, Desheng, Pandey, Ratnesh, Tungare, Kunal, Friedrich, Kristian, Mehzabeen, Nurjahan, Biancucci, Marco, Chinchilla-Olszar, Diana, Mallett, Corey P., Huang, Ying, Wang, Zihao, Bottomley, Matthew James, Malito, Enrico, Chandramouli, Sumana
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.11.2020; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antigenic determinants; Antigens; At risk populations; Biology and Life Sciences; Calcium channels (voltage-gated); Cattle; Cell membranes; Competition; Crystal structure; Crystallography, X-Ray; Elongated structure; Epitopes; Epitopes - immunology; F protein; Fab; Humans; Immune response; Immunization; Immunogenicity; Immunogenicity, Vaccine - immunology; Infants; Insertion; Interferometry; Medicine and Health Sciences; Models, Structural; N-Terminus; Neutralizing; Peptides; Physical Sciences; Physiological aspects; Proteins; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Vaccines - immunology; Respiratory Syncytial Viruses - immunology; Risk groups; Structure; Vaccines; Viral Fusion Proteins - immunology; Viruses; United States
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1008943

Respiratory syncytial virus (RSV) is a global public health burden for which no licensed vaccine exists. To aid vaccine development via increased understanding of the protective antibody response to RSV prefusion glycoprotein F (PreF), we performed structural and functional studies using the human neutralizing antibody (nAb) RSB1. The crystal structure of PreF complexed with RSB1 reveals a conformational, pre-fusion specific site V epitope with a unique cross-protomer binding mechanism. We identify shared structural features between nAbs RSB1 and CR9501, elucidating for the first time how diverse germlines obtained from different subjects can develop convergent molecular mechanisms for recognition of the same PreF site of vulnerability. Importantly, RSB1-like nAbs were induced upon immunization with PreF in naturally-primed cattle. Together, this work reveals new details underlying the immunogenicity of site V and further supports PreF-based vaccine development efforts.