Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation

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 mo...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2018-02, Vol.48 (2), p.339-349.e5
Main Authors: Goodwin, Eileen, Gilman, Morgan S.A., Wrapp, Daniel, Chen, Man, Ngwuta, Joan O., Moin, Syed M., Bai, Patricia, Sivasubramanian, Arvind, Connor, Ruth I., Wright, Peter F., Graham, Barney S., McLellan, Jason S., Walker, Laura M.
Format: Article
Language:English
Subjects:
Age
Animals
Antibodies
Antibodies, Neutralizing - biosynthesis
Antibodies, Viral - biosynthesis
Antigens
B-Lymphocytes - immunology
Babies
BASIC BIOLOGICAL SCIENCES
Binding sites
Clinical trials
crystal structures
germline
Glycoproteins
Humans
IGHV3-11:IGLV1-40
IGHV3-21:IGLV1-40
Immunoglobulins
Immunology
Infant
Infant mortality
Infants
Infections
Lymphocytes B
Mice
Monoclonal antibodies
Mutation
naive B cells
Neutralizing
pneumoviridae
Respiratory syncytial virus
Respiratory Syncytial Virus Infections - immunology
Respiratory Syncytial Virus Vaccines - immunology
Somatic hypermutation
Somatic Hypermutation, Immunoglobulin
Studies
Vaccine development
Vaccines
Viral Fusion Proteins - immunology
Viruses
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Summary: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. [Display omitted] •Isolated more than 450 antibodies from seven RSV-infected infants•Discovered potent neutralizing antibodies that lack somatic hypermutation•Identified similar antibodies from RSV-naive repertoires•Delineated the structural basis for germline-mediated recognition of RSV F An increased understanding of infant antibody responses to RSV infection would greatly facilitate vaccine development. Goodwin et al. isolate and structurally characterize antibodies from RSV-infected infants and identify potent neutralizing antibodies that lack somatic hypermutation. The results provide a framework for the rational design of age-specific RSV vaccines.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2018.01.005