Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site

Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutraliz...

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Vydáno v:	Cell reports (Cambridge) Ročník 14; číslo 1; s. 43 - 54
Hlavní autoři:	Bradley, Todd, Fera, Daniela, Bhiman, Jinal, Eslamizar, Leila, Lu, Xiaozhi, Anasti, Kara, Zhang, Ruijung, Sutherland, Laura L., Scearce, Richard M., Bowman, Cindy M., Stolarchuk, Christina, Lloyd, Krissey E., Parks, Robert, Eaton, Amanda, Foulger, Andrew, Nie, Xiaoyan, Karim, Salim S. Abdool, Barnett, Susan, Kelsoe, Garnett, Kepler, Thomas B., Alam, S. Munir, Montefiori, David C., Moody, M. Anthony, Liao, Hua-Xin, Morris, Lynn, Santra, Sampa, Harrison, Stephen C., Haynes, Barton F.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Elsevier Inc 05.01.2016 Elsevier
Témata:	AIDS Vaccines - immunology AIDS Vaccines - pharmacology Amino Acid Sequence Animals Antibodies, Neutralizing - immunology BASIC BIOLOGICAL SCIENCES env Gene Products, Human Immunodeficiency Virus - genetics env Gene Products, Human Immunodeficiency Virus - immunology Female HIV Antibodies - immunology HIV-1 - genetics HIV-1 - immunology Humans Macaca mulatta Male Molecular Sequence Data
ISSN:	2211-1247, 2211-1247
On-line přístup:	Získat plný text
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Popis
Shrnutí:	Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization. [Display omitted] •HIV-1 TF Env immunization induced potent Tier-2 neutralizing antibodies (nAbs)•Vaccine-elicited nAbs target CD4bs and mimic autologous nAbs in infected individual•Autologous nAb-Env complex structure reveals mechanism of strain-specific neutralization HIV-1 vaccine elicitation of antibodies against neutralization-resistant (Tier-2) viruses is rare. Bradley et al. demonstrate induction of antibodies that can neutralize a vaccine-matched Tier-2 virus in a rhesus macaque immunized with HIV trimers isolated from a HIV-1-infected individual. Structural analysis revealed the mechanism of restricted neutralization breadth.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 1F32AI116355-01 NIH/NIAID/DAIDS Co-first author
ISSN:	2211-1247 2211-1247
DOI:	10.1016/j.celrep.2015.12.017