6APB

Crystal Structure of Non-Neutralizing Infant Antibody ADI-14359 in Complex with Postfusion RSV F Glycoprotein

Summary for 6APB

• Entry DOI: 10.2210/pdb6apb/pdb
• Descriptor: Fusion glycoprotein F0,Fusion glycoprotein F0, IgG H chain, ADI-14359 Fab Light Chain, ... (4 entities in total)
• Functional Keywords: viral fusion glycoprotein, immunoglobulin, respiratory syncytial virus, immune system
• Biological source: Human respiratory syncytial virus; More
• Total number of polymer chains: 5
• Total formula weight: 219044.04

Authors

Gilman, M.S.A.,McLellan, J.S. (deposition date: 2017-08-17, release date: 2018-03-21, Last modification date: 2024-11-06)

Primary citation

Goodwin, E.,Gilman, M.S.A.,Wrapp, D.,Chen, M.,Ngwuta, J.O.,Moin, S.M.,Bai, P.,Sivasubramanian, A.,Connor, R.I.,Wright, P.F.,Graham, B.S.,McLellan, J.S.,Walker, L.M.
Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation.
Immunity, 48:339-349.e5, 2018

PubMed Abstract: Respiratory syncytial virus (RSV) is a leading cause of infant mortality, and there are currently no licensed vaccines to protect this vulnerable population. A comprehensive understanding of infant antibody responses to natural RSV infection would facilitate vaccine development. Here, we isolated more than 450 RSV fusion glycoprotein (F)-specific antibodies from 7 RSV-infected infants and found that half of the antibodies recognized only two antigenic sites. Antibodies targeting both sites showed convergent sequence features, and structural studies revealed the molecular basis for their recognition of RSV F. A subset of antibodies targeting one of these sites displayed potent neutralizing activity despite lacking somatic mutations, and similar antibodies were detected in RSV-naive B cell repertoires, suggesting that expansion of these B cells in infants may be possible with suitably designed vaccine antigens. Collectively, our results provide fundamental insights into infant antibody responses and a framework for the rational design of age-specific RSV vaccines.

PubMed: 29396163
DOI: 10.1016/j.immuni.2018.01.005

Experimental method

X-RAY DIFFRACTION (3 Å)