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Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates.
Steichen, Jon M; Phung, Ivy; Salcedo, Eugenia; Ozorowski, Gabriel; Willis, Jordan R; Baboo, Sabyasachi; Liguori, Alessia; Cottrell, Christopher A; Torres, Jonathan L; Madden, Patrick J; Ma, Krystal M; Sutton, Henry J; Lee, Jeong Hyun; Kalyuzhniy, Oleksandr; Allen, Joel D; Rodriguez, Oscar L; Adachi, Yumiko; Mullen, Tina-Marie; Georgeson, Erik; Kubitz, Michael; Burns, Alison; Barman, Shawn; Mopuri, Rohini; Metz, Amanda; Altheide, Tasha K; Diedrich, Jolene K; Saha, Swati; Shields, Kaitlyn; Schultze, Steven E; Smith, Melissa L; Schiffner, Torben; Burton, Dennis R; Watson, Corey T; Bosinger, Steven E; Crispin, Max; Yates, John R; Paulson, James C; Ward, Andrew B; Sok, Devin; Crotty, Shane; Schief, William R.
Afiliação
  • Steichen JM; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Phung I; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Salcedo E; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Ozorowski G; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Willis JR; Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Baboo S; Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
  • Liguori A; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Cottrell CA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Torres JL; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Madden PJ; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Ma KM; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Sutton HJ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Lee JH; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Kalyuzhniy O; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Allen JD; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Rodriguez OL; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Adachi Y; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Mullen TM; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Georgeson E; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Kubitz M; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Burns A; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Barman S; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Mopuri R; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Metz A; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Altheide TK; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Diedrich JK; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Saha S; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Shields K; Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Schultze SE; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Smith ML; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Schiffner T; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Burton DR; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Watson CT; Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Bosinger SE; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Crispin M; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Yates JR; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Paulson JC; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Ward AB; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Sok D; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Crotty S; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Schief WR; School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Science ; 384(6697): eadj8321, 2024 May 17.
Article em En | MEDLINE | ID: mdl-38753769
ABSTRACT
Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / Vacinas contra a AIDS / Centro Germinativo / Regiões Determinantes de Complementaridade / Anticorpos Amplamente Neutralizantes Limite: Animals / Humans Idioma: En Revista: Science Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / Vacinas contra a AIDS / Centro Germinativo / Regiões Determinantes de Complementaridade / Anticorpos Amplamente Neutralizantes Limite: Animals / Humans Idioma: En Revista: Science Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos