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Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1
A central goal of HIV-1-vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component of the viral entry machinery and the epitope...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358635/ https://www.ncbi.nlm.nih.gov/pubmed/29867235 http://dx.doi.org/10.1038/s41591-018-0042-6 |
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author | Xu, Kai Acharya, Priyamvada Kong, Rui Cheng, Cheng Chuang, Gwo-Yu Liu, Kevin Louder, Mark K. O’Dell, Sijy Rawi, Reda Sastry, Mallika Shen, Chen-Hsiang Zhang, Baoshan Zhou, Tongqing Asokan, Mangaiarkarasi Bailer, Robert T. Chambers, Michael Chen, Xuejun Choi, Chang W. Dandey, Venkata P. Doria-Rose, Nicole A. Druz, Aliaksandr Eng, Edward T. Farney, Katie Foulds, Kathryn E. Geng, Hui Georgiev, Ivelin S. Gorman, Jason Hill, Kurt R. Jafari, Alexander J. Kwon, Young D. Lai, Yen-Ting Lemmin, Thomas McKee, Krisha Ohr, Tiffany Y. Ou, Li Peng, Dongjun Rowshan, Ariana P. Sheng, Zizhang Todd, John-Paul Tsybovsky, Yaroslav Viox, Elise G. Wang, Yiran Wei, Hui Yang, Yongping Zhou, Amy F. Chen, Rui Yang, Lu Scorpio, Diana G. McDermott, Adrian B. Shapiro, Lawrence Carragher, Bridget Potter, Clinton S. Mascola, John R. Kwong, Peter D. |
author_facet | Xu, Kai Acharya, Priyamvada Kong, Rui Cheng, Cheng Chuang, Gwo-Yu Liu, Kevin Louder, Mark K. O’Dell, Sijy Rawi, Reda Sastry, Mallika Shen, Chen-Hsiang Zhang, Baoshan Zhou, Tongqing Asokan, Mangaiarkarasi Bailer, Robert T. Chambers, Michael Chen, Xuejun Choi, Chang W. Dandey, Venkata P. Doria-Rose, Nicole A. Druz, Aliaksandr Eng, Edward T. Farney, Katie Foulds, Kathryn E. Geng, Hui Georgiev, Ivelin S. Gorman, Jason Hill, Kurt R. Jafari, Alexander J. Kwon, Young D. Lai, Yen-Ting Lemmin, Thomas McKee, Krisha Ohr, Tiffany Y. Ou, Li Peng, Dongjun Rowshan, Ariana P. Sheng, Zizhang Todd, John-Paul Tsybovsky, Yaroslav Viox, Elise G. Wang, Yiran Wei, Hui Yang, Yongping Zhou, Amy F. Chen, Rui Yang, Lu Scorpio, Diana G. McDermott, Adrian B. Shapiro, Lawrence Carragher, Bridget Potter, Clinton S. Mascola, John R. Kwong, Peter D. |
author_sort | Xu, Kai |
collection | PubMed |
description | A central goal of HIV-1-vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component of the viral entry machinery and the epitope of antibodies elicited by HIV-1 infection, through immunization with fusion peptide-coupled carriers and prefusion-stabilized envelope trimers, induces cross-clade neutralizing responses. In mice, these immunogens elicited monoclonal antibodies capable of neutralizing up to 31% of a cross-clade panel of 208 HIV-1 strains. Crystal and cryo-electron microscopy structures of these antibodies revealed fusion peptide-conformational diversity as a molecular explanation for the cross-clade neutralization. Immunization of guinea pigs and rhesus macaques induced similarly broad fusion peptide-directed neutralizing responses suggesting translatability. The N terminus of the HIV-1-fusion peptide is thus a promising target of vaccine efforts aimed at eliciting broadly neutralizing antibodies. |
format | Online Article Text |
id | pubmed-6358635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
record_format | MEDLINE/PubMed |
spelling | pubmed-63586352019-02-02 Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1 Xu, Kai Acharya, Priyamvada Kong, Rui Cheng, Cheng Chuang, Gwo-Yu Liu, Kevin Louder, Mark K. O’Dell, Sijy Rawi, Reda Sastry, Mallika Shen, Chen-Hsiang Zhang, Baoshan Zhou, Tongqing Asokan, Mangaiarkarasi Bailer, Robert T. Chambers, Michael Chen, Xuejun Choi, Chang W. Dandey, Venkata P. Doria-Rose, Nicole A. Druz, Aliaksandr Eng, Edward T. Farney, Katie Foulds, Kathryn E. Geng, Hui Georgiev, Ivelin S. Gorman, Jason Hill, Kurt R. Jafari, Alexander J. Kwon, Young D. Lai, Yen-Ting Lemmin, Thomas McKee, Krisha Ohr, Tiffany Y. Ou, Li Peng, Dongjun Rowshan, Ariana P. Sheng, Zizhang Todd, John-Paul Tsybovsky, Yaroslav Viox, Elise G. Wang, Yiran Wei, Hui Yang, Yongping Zhou, Amy F. Chen, Rui Yang, Lu Scorpio, Diana G. McDermott, Adrian B. Shapiro, Lawrence Carragher, Bridget Potter, Clinton S. Mascola, John R. Kwong, Peter D. Nat Med Article A central goal of HIV-1-vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component of the viral entry machinery and the epitope of antibodies elicited by HIV-1 infection, through immunization with fusion peptide-coupled carriers and prefusion-stabilized envelope trimers, induces cross-clade neutralizing responses. In mice, these immunogens elicited monoclonal antibodies capable of neutralizing up to 31% of a cross-clade panel of 208 HIV-1 strains. Crystal and cryo-electron microscopy structures of these antibodies revealed fusion peptide-conformational diversity as a molecular explanation for the cross-clade neutralization. Immunization of guinea pigs and rhesus macaques induced similarly broad fusion peptide-directed neutralizing responses suggesting translatability. The N terminus of the HIV-1-fusion peptide is thus a promising target of vaccine efforts aimed at eliciting broadly neutralizing antibodies. 2018-06-04 2018-06 /pmc/articles/PMC6358635/ /pubmed/29867235 http://dx.doi.org/10.1038/s41591-018-0042-6 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Xu, Kai Acharya, Priyamvada Kong, Rui Cheng, Cheng Chuang, Gwo-Yu Liu, Kevin Louder, Mark K. O’Dell, Sijy Rawi, Reda Sastry, Mallika Shen, Chen-Hsiang Zhang, Baoshan Zhou, Tongqing Asokan, Mangaiarkarasi Bailer, Robert T. Chambers, Michael Chen, Xuejun Choi, Chang W. Dandey, Venkata P. Doria-Rose, Nicole A. Druz, Aliaksandr Eng, Edward T. Farney, Katie Foulds, Kathryn E. Geng, Hui Georgiev, Ivelin S. Gorman, Jason Hill, Kurt R. Jafari, Alexander J. Kwon, Young D. Lai, Yen-Ting Lemmin, Thomas McKee, Krisha Ohr, Tiffany Y. Ou, Li Peng, Dongjun Rowshan, Ariana P. Sheng, Zizhang Todd, John-Paul Tsybovsky, Yaroslav Viox, Elise G. Wang, Yiran Wei, Hui Yang, Yongping Zhou, Amy F. Chen, Rui Yang, Lu Scorpio, Diana G. McDermott, Adrian B. Shapiro, Lawrence Carragher, Bridget Potter, Clinton S. Mascola, John R. Kwong, Peter D. Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1 |
title | Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1 |
title_full | Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1 |
title_fullStr | Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1 |
title_full_unstemmed | Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1 |
title_short | Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1 |
title_sort | epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of hiv-1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358635/ https://www.ncbi.nlm.nih.gov/pubmed/29867235 http://dx.doi.org/10.1038/s41591-018-0042-6 |
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