Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation
While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engine...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-04-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717304886 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Tongqing Zhou Nicole A. Doria-Rose Cheng Cheng Guillaume B.E. Stewart-Jones Gwo-Yu Chuang Michael Chambers Aliaksandr Druz Hui Geng Krisha McKee Young Do Kwon Sijy O’Dell Mallika Sastry Stephen D. Schmidt Kai Xu Lei Chen Rita E. Chen Mark K. Louder Marie Pancera Timothy G. Wanninger Baoshan Zhang Anqi Zheng S. Katie Farney Kathryn E. Foulds Ivelin S. Georgiev M. Gordon Joyce Thomas Lemmin Sandeep Narpala Reda Rawi Cinque Soto John-Paul Todd Chen-Hsiang Shen Yaroslav Tsybovsky Yongping Yang Peng Zhao Barton F. Haynes Leonidas Stamatatos Michael Tiemeyer Lance Wells Diana G. Scorpio Lawrence Shapiro Adrian B. McDermott John R. Mascola Peter D. Kwong |
| spellingShingle |
Tongqing Zhou Nicole A. Doria-Rose Cheng Cheng Guillaume B.E. Stewart-Jones Gwo-Yu Chuang Michael Chambers Aliaksandr Druz Hui Geng Krisha McKee Young Do Kwon Sijy O’Dell Mallika Sastry Stephen D. Schmidt Kai Xu Lei Chen Rita E. Chen Mark K. Louder Marie Pancera Timothy G. Wanninger Baoshan Zhang Anqi Zheng S. Katie Farney Kathryn E. Foulds Ivelin S. Georgiev M. Gordon Joyce Thomas Lemmin Sandeep Narpala Reda Rawi Cinque Soto John-Paul Todd Chen-Hsiang Shen Yaroslav Tsybovsky Yongping Yang Peng Zhao Barton F. Haynes Leonidas Stamatatos Michael Tiemeyer Lance Wells Diana G. Scorpio Lawrence Shapiro Adrian B. McDermott John R. Mascola Peter D. Kwong Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation Cell Reports CD4-binding site crystal structure envelope glycoprotein glycan shield glycomics HIV-1 immunogen design immunogenicity targeted deglycosylation vaccine design |
| author_facet |
Tongqing Zhou Nicole A. Doria-Rose Cheng Cheng Guillaume B.E. Stewart-Jones Gwo-Yu Chuang Michael Chambers Aliaksandr Druz Hui Geng Krisha McKee Young Do Kwon Sijy O’Dell Mallika Sastry Stephen D. Schmidt Kai Xu Lei Chen Rita E. Chen Mark K. Louder Marie Pancera Timothy G. Wanninger Baoshan Zhang Anqi Zheng S. Katie Farney Kathryn E. Foulds Ivelin S. Georgiev M. Gordon Joyce Thomas Lemmin Sandeep Narpala Reda Rawi Cinque Soto John-Paul Todd Chen-Hsiang Shen Yaroslav Tsybovsky Yongping Yang Peng Zhao Barton F. Haynes Leonidas Stamatatos Michael Tiemeyer Lance Wells Diana G. Scorpio Lawrence Shapiro Adrian B. McDermott John R. Mascola Peter D. Kwong |
| author_sort |
Tongqing Zhou |
| title |
Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation |
| title_short |
Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation |
| title_full |
Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation |
| title_fullStr |
Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation |
| title_full_unstemmed |
Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation |
| title_sort |
quantification of the impact of the hiv-1-glycan shield on antibody elicitation |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2017-04-01 |
| description |
While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character). To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID50) proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies. |
| topic |
CD4-binding site crystal structure envelope glycoprotein glycan shield glycomics HIV-1 immunogen design immunogenicity targeted deglycosylation vaccine design |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124717304886 |
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1725150341528289280 |
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doaj-aabe08812b3841a8a0593b8fc0b383552020-11-25T01:16:17ZengElsevierCell Reports2211-12472017-04-0119471973210.1016/j.celrep.2017.04.013Quantification of the Impact of the HIV-1-Glycan Shield on Antibody ElicitationTongqing Zhou0Nicole A. Doria-Rose1Cheng Cheng2Guillaume B.E. Stewart-Jones3Gwo-Yu Chuang4Michael Chambers5Aliaksandr Druz6Hui Geng7Krisha McKee8Young Do Kwon9Sijy O’Dell10Mallika Sastry11Stephen D. Schmidt12Kai Xu13Lei Chen14Rita E. Chen15Mark K. Louder16Marie Pancera17Timothy G. Wanninger18Baoshan Zhang19Anqi Zheng20S. Katie Farney21Kathryn E. Foulds22Ivelin S. Georgiev23M. Gordon Joyce24Thomas Lemmin25Sandeep Narpala26Reda Rawi27Cinque Soto28John-Paul Todd29Chen-Hsiang Shen30Yaroslav Tsybovsky31Yongping Yang32Peng Zhao33Barton F. Haynes34Leonidas Stamatatos35Michael Tiemeyer36Lance Wells37Diana G. Scorpio38Lawrence Shapiro39Adrian B. McDermott40John R. Mascola41Peter D. Kwong42Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAElectron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAComplex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USADuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, P.O. Box 19024, Seattle, WA 98109, USAComplex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USAComplex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAWhile the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character). To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID50) proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies.http://www.sciencedirect.com/science/article/pii/S2211124717304886CD4-binding sitecrystal structureenvelope glycoproteinglycan shieldglycomicsHIV-1immunogen designimmunogenicitytargeted deglycosylationvaccine design |