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Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies.
Sahoo, Anusmita; Hodge, Edgar A; LaBranche, Celia C; Styles, Tiffany M; Shen, Xiaoying; Cheedarla, Narayanaiah; Shiferaw, Ayalnesh; Ozorowski, Gabriel; Lee, Wen-Hsin; Ward, Andrew B; Tomaras, Georgia D; Montefiori, David C; Irvine, Darrell J; Lee, Kelly K; Amara, Rama Rao.
Affiliation
  • Sahoo A; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Hodge EA; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
  • LaBranche CC; Department of Surgery, Duke University Medical School, Duke University, Durham, NC 27710, USA.
  • Styles TM; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Shen X; Department of Surgery, Duke University Medical School, Duke University, Durham, NC 27710, USA.
  • Cheedarla N; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Shiferaw A; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Ozorowski G; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, San Diego, CA 92121, USA.
  • Lee WH; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, San Diego, CA 92121, USA.
  • Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, San Diego, CA 92121, USA.
  • Tomaras GD; Department of Surgery, Duke University Medical School, Duke University, Durham, NC 27710, USA.
  • Montefiori DC; Department of Surgery, Duke University Medical School, Duke University, Durham, NC 27710, USA.
  • Irvine DJ; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Lee KK; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
  • Amara RR; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: ramara@emory.edu.
Cell Rep ; 38(9): 110436, 2022 03 01.
Article in En | MEDLINE | ID: mdl-35235790
ABSTRACT
HIV-1 clade C envelope immunogens that elicit both neutralizing and non-neutralizing V1V2-scaffold-specific antibodies (protective correlates from RV144 human trial) are urgently needed due to the prevalence of this clade in the most impacted regions worldwide. To achieve this, we introduce structure-guided changes followed by consensus-C-sequence-guided optimizations at the V2 region to generate UFO-v2-RQH173 trimer. This improves the abundance of well-formed trimers. Following the immunization of rabbits, the wild-type protein fails to elicit any autologous neutralizing antibodies, but UFO-v2-RQH173 elicits both autologous neutralizing and broad V1V2-scaffold antibodies. The variant with a 173Y modification in the V2 region, most prevalent among HIV-1 sequences, shows decreased ability in displaying a native-like V1V2 epitope with time in vitro and elicited antibodies with lower neutralizing and higher V1V2-scaffold activities. Our results identify a stabilized clade C trimer capable of eliciting improved neutralizing and V1V2-scaffold antibodies and reveal the importance of the V2 region in tuning this.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Infections / HIV-1 / HIV Seropositivity / AIDS Vaccines Type of study: Risk_factors_studies Limits: Animals Language: En Journal: Cell Rep Year: 2022 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Infections / HIV-1 / HIV Seropositivity / AIDS Vaccines Type of study: Risk_factors_studies Limits: Animals Language: En Journal: Cell Rep Year: 2022 Document type: Article Affiliation country: