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Disassembly of HIV envelope glycoprotein trimer immunogens is driven by antibodies elicited via immunization.
Turner, Hannah L; Andrabi, Raiees; Cottrell, Christopher A; Richey, Sara T; Song, Ge; Callaghan, Sean; Anzanello, Fabio; Moyer, Tyson J; Abraham, Wuhbet; Melo, Mariane; Silva, Murillo; Scaringi, Nicole; Rakasz, Eva G; Sattentau, Quentin J; Irvine, Darrell J; Burton, Dennis R; Ward, Andrew B.
Afiliación
  • Turner HL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Andrabi R; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Cottrell CA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Richey ST; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Song G; International AIDS Vaccine Initiative-Neutralizing Antibody Center (IAVI-NAC), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Callaghan S; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Anzanello F; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Moyer TJ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Abraham W; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Melo M; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Silva M; International AIDS Vaccine Initiative-Neutralizing Antibody Center (IAVI-NAC), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Scaringi N; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Rakasz EG; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Sattentau QJ; International AIDS Vaccine Initiative-Neutralizing Antibody Center (IAVI-NAC), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Irvine DJ; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Burton DR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Ward AB; International AIDS Vaccine Initiative-Neutralizing Antibody Center (IAVI-NAC), The Scripps Research Institute, La Jolla, CA 92037, USA.
Sci Adv ; 7(31)2021 07.
Article en En | MEDLINE | ID: mdl-34321200
Rationally designed protein subunit vaccines are being developed for a variety of viruses including influenza, RSV, SARS-CoV-2, and HIV. These vaccines are based on stabilized versions of the primary targets of neutralizing antibodies on the viral surface, namely, viral fusion glycoproteins. While these immunogens display the epitopes of potent neutralizing antibodies, they also present epitopes recognized by non-neutralizing or weakly neutralizing ("off-target") antibodies. Using our recently developed electron microscopy polyclonal epitope mapping approach, we have uncovered a phenomenon wherein off-target antibodies elicited by HIV trimer subunit vaccines cause the otherwise highly stabilized trimeric proteins to degrade into cognate protomers. Further, we show that these protomers expose an expanded suite of off-target epitopes, normally occluded inside the prefusion conformation of trimer, that subsequently elicit further off-target antibody responses. Our study provides critical insights for further improvement of HIV subunit trimer vaccines for future rounds of the iterative vaccine design process.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Anti-VIH / Infecciones por VIH / VIH-1 / Vacunas contra el SIDA / Productos del Gen env del Virus de la Inmunodeficiencia Humana Límite: Animals / Female / Humans Idioma: En Revista: Sci Adv Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Anti-VIH / Infecciones por VIH / VIH-1 / Vacunas contra el SIDA / Productos del Gen env del Virus de la Inmunodeficiencia Humana Límite: Animals / Female / Humans Idioma: En Revista: Sci Adv Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos