Structural basis for nonneutralizing antibody competition at antigenic site II of the respiratory syncytial virus fusion protein

• DOI: 10.1073/pnas.1609449113
• Publication Date: 2016-10-18T20:37:54Z
• Authors: Jarrod J. Mousa; Marion F. Sauer; Alexander M. Sevy; Jessica A. Finn; John T. Bates; Gabriela Alvarado; Hannah G. King; Leah B. Loerinc; Rachel H. Fong; Benjamin J. Doranz; Bruno E. Correia; Oleksandr Kalyuzhniy; Xiaolin Wen; Theodore S. Jarde...; William R. Schief; Melanie D. Ohi; Jens Meiler; James E. Crowe
• Keywords: Palivizumab; A-site

Significance Respiratory syncytial virus is a highly contagious human pathogen, infecting the majority of infants before age 2 y, and leading cause viral bronchiolitis pneumonia in children. An approved prophylactic humanized mouse monoclonal antibody, palivizumab, currently standard-of-care treatment for immunocompromised individuals, competition with palivizumab has been proposed as basis measuring effective immune responses vaccine trials. Using combination X-ray crystallography, hydrogen-deuterium exchange, saturation alanine mutagenesis scanning, we show structural neutralization by antibody at antigenic site. Furthermore, describe nonneutralizing antibodies that directly compete another 14N4. Taken together, data presented provide unique concepts structure-based design.