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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, S 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.
Afiliación
  • Xu K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Acharya P; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Kong R; National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY, USA.
  • Cheng C; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Chuang GY; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Liu K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Louder MK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • O'Dell S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Rawi R; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Sastry M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Shen CH; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Zhang B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Zhou T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Asokan M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Bailer RT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Chambers M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Chen X; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Choi CW; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Dandey VP; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Doria-Rose NA; National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY, USA.
  • Druz A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Eng ET; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Farney SK; National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY, USA.
  • Foulds KE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Geng H; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Georgiev IS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Gorman J; Vanderbilt Vaccine Center, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, and Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN, USA.
  • Hill KR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Jafari AJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Kwon YD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Lai YT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Lemmin T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • McKee K; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
  • Ohr TY; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Ou L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Peng D; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Rowshan AP; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Sheng Z; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Todd JP; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
  • Tsybovsky Y; Department of Systems Biology, Columbia University, New York, NY, USA.
  • Viox EG; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Wang Y; Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
  • Wei H; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Yang Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Zhou AF; National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY, USA.
  • Chen R; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Yang L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Scorpio DG; GenScript USA, Piscataway, NJ, USA.
  • McDermott AB; GenScript USA, Piscataway, NJ, USA.
  • Shapiro L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Nat Med ; 24(6): 857-867, 2018 06.
Article en En | MEDLINE | ID: mdl-29867235
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 cryoelectron 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.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Péptidos / Proteínas Recombinantes de Fusión / Anticuerpos Anti-VIH / VIH-1 / Vacunas contra el SIDA / Anticuerpos Neutralizantes / Epítopos Límite: Animals Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Péptidos / Proteínas Recombinantes de Fusión / Anticuerpos Anti-VIH / VIH-1 / Vacunas contra el SIDA / Anticuerpos Neutralizantes / Epítopos Límite: Animals Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos