Crystal Structure and Immunogenicity of the DS-Cav1-Stabilized Fusion Glycoprotein From Respiratory Syncytial Virus Subtype B Article Swipe
Michael Joyce
,
Amy Bao
,
Man Chen
,
Ivelin S. Georgiev
,
Li Ou
,
Tatsiana Bylund
,
Aliaksandr Druz
,
Wing‐Pui Kong
,
Dongjun Peng
,
Emily J. Rundlet
,
Joseph G. Van Galen
,
Shuishu Wang
,
Yongping Yang
,
Baoshan Zhang
,
Gwo‐Yu Chuang
,
Jason S. McLellan
,
Barney S. Graham
,
John R. Mascola
,
Peter D. Kwong
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.20411/pai.v4i2.338
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.20411/pai.v4i2.338
Background: Respiratory syncytial virus (RSV) subtypes, A and B, co-circulate in annual epidemics and alternate in dominance. We have shown that a subtype A RSV fusion (F) glycoprotein, stabilized in its prefusion conformation by DS-Cav1 mutations, is a promising RSV-vaccine immunogen, capable of boosting RSV-neutralizing titers in healthy adults. In both humans and vaccine-tested animals, neutralizing titers elicited by this subtype A DS-Cav1 immunogen were ~ 2- to 3-fold higher against the homologous subtype A virus than against the heterologous subtype B virus.Methods: To understand the molecular basis for this subtype difference, we introduced DS-Cav1 mutations into RSV strain B18537 F, determined the trimeric crystal structure, and carried out immunogenicity studies.Results: The B18537 DS-Cav1 F structure at 2-Å resolution afforded a precise delineation of prefusion F characteristics, including those of antigenic site Ø, a key trimer-apex site. Structural comparison with the subtype A prefusion F indicated 11% of surface residues to be different, with an alpha-carbon root-mean-square deviation (RMSD) of 1.2 Å; antigenic site Ø, however, resulted in 23% of its surface residues and had an alpha-carbon RMSD of 2.2 Å. Immunization of vaccine-tested animals with DS-Cav1-stabilized B18537 F induced neutralizing responses ~100-fold higher than with postfusion B18537 F. Notably, elicited responses neutralized RSV subtypes A and B at similar levels and were directed towards both conserved equatorial and diverse apical regions.Conclusion: We propose that structural differences in apical and equatorial sites–coupled to differently focused immune responses–provide a molecular explanation for observed differences in elicited subtype A and B neutralizing responses.Keywords: antigenic site; crystal structure; epitope; fusion glycoprotein; immunogenicity; neutralization; RSV subtype; vaccine
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.20411/pai.v4i2.338
- https://paijournal.com/index.php/paijournal/article/download/338/235
- OA Status
- diamond
- Cited By
- 33
- References
- 77
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4231251043
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4231251043Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.20411/pai.v4i2.338Digital Object Identifier
- Title
-
Crystal Structure and Immunogenicity of the DS-Cav1-Stabilized Fusion Glycoprotein From Respiratory Syncytial Virus Subtype BWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-12-11Full publication date if available
- Authors
-
Michael Joyce, Amy Bao, Man Chen, Ivelin S. Georgiev, Li Ou, Tatsiana Bylund, Aliaksandr Druz, Wing‐Pui Kong, Dongjun Peng, Emily J. Rundlet, Joseph G. Van Galen, Shuishu Wang, Yongping Yang, Baoshan Zhang, Gwo‐Yu Chuang, Jason S. McLellan, Barney S. Graham, John R. Mascola, Peter D. KwongList of authors in order
- Landing page
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https://doi.org/10.20411/pai.v4i2.338Publisher landing page
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https://paijournal.com/index.php/paijournal/article/download/338/235Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
diamondOpen access status per OpenAlex
- OA URL
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https://paijournal.com/index.php/paijournal/article/download/338/235Direct OA link when available
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Immunogen, Immunogenicity, Virology, Biology, Virus, Titer, Neutralizing antibody, Heterologous, Vero cell, Antigen, Antibody, Gene, Immunology, Genetics, Monoclonal antibodyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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33Total citation count in OpenAlex
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2025: 1, 2024: 4, 2023: 13, 2022: 5, 2021: 6Per-year citation counts (last 5 years)
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77Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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