Binding of inferred germline precursors of broadly neutralizing HIV-1 antibodies to native-like envelope trimers

Kwinten Sliepen; Max Medina-Ramírez; Anila Yasmeen; John P Moore; Per Johan Klasse; Rogier W Sanders

doi:10.1016/j.virol.2015.08.002

Binding of inferred germline precursors of broadly neutralizing HIV-1 antibodies to native-like envelope trimers

Virology. 2015 Dec:486:116-20. doi: 10.1016/j.virol.2015.08.002. Epub 2015 Oct 1.

Authors

Kwinten Sliepen¹, Max Medina-Ramírez², Anila Yasmeen³, John P Moore⁴, Per Johan Klasse⁵, Rogier W Sanders⁶

Affiliations

¹ Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. Electronic address: k.h.sliepen@amc.uva.nl.
² Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. Electronic address: j.m.medinaramirez@amc.uva.nl.
³ Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA. Electronic address: yasmeenanila1@gmail.com.
⁴ Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA. Electronic address: pek2003@med.cornell.edu.
⁵ Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA. Electronic address: jpm2003@med.cornell.edu.
⁶ Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA. Electronic address: r.w.sanders@amc.uva.nl.

Abstract

HIV-1 envelope glycoproteins (Env) and Env-based immunogens usually do not interact efficiently with the inferred germline precursors of known broadly neutralizing antibodies (bNAbs). This deficiency may be one reason why Env and Env-based immunogens are not efficient at inducing bNAbs. We evaluated the binding of 15 inferred germline precursors of bNAbs directed to different epitope clusters to three soluble native-like SOSIP.664 Env trimers. We found that native-like SOSIP.664 trimers bind to some inferred germline precursors of bNAbs, particularly ones involving the V1/V2 loops at the apex of the trimer. The data imply that native-like SOSIP.664 trimers will be an appropriate platform for structure-guided design improvements intended to create immunogens able to target the germline precursors of bNAbs.

Keywords: Broadly neutralizing antibodies; Env; Germline; HIV-1; SOSIP; Vaccine.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Neutralizing / immunology*
HIV Antibodies / immunology*
HIV Infections / immunology*
HIV Infections / virology
HIV-1 / chemistry
HIV-1 / immunology*
Humans
env Gene Products, Human Immunodeficiency Virus / chemistry
env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

Antibodies, Neutralizing
HIV Antibodies
env Gene Products, Human Immunodeficiency Virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding