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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
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.
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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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