Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design

Raiees Andrabi; James E Voss; Chi-Hui Liang; Bryan Briney; Laura E McCoy; Chung-Yi Wu; Chi-Huey Wong; Pascal Poignard; Dennis R Burton

doi:10.1016/j.immuni.2015.10.014

Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design

Immunity. 2015 Nov 17;43(5):959-73. doi: 10.1016/j.immuni.2015.10.014.

Authors

Raiees Andrabi¹, James E Voss¹, Chi-Hui Liang¹, Bryan Briney¹, Laura E McCoy¹, Chung-Yi Wu², Chi-Huey Wong², Pascal Poignard³, Dennis R Burton⁴

Affiliations

¹ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
² Genomics Research Center, Academia Sinica, Nankang, Taipei 115, Taiwan.
³ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁴ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02114, USA. Electronic address: [email protected].

Abstract

Broadly neutralizing antibodies (bnAbs) directed to the V2 apex of the HIV envelope (Env) trimer isolated from individual HIV-infected donors potently neutralize diverse HIV strains, but strategies for designing immunogens to elicit bnAbs have not been identified. Here, we compared four prototypes (PG9, CH01, PGT145, and CAP256.VRC26.09) of V2 apex bnAbs and showed that all recognized a core epitope of basic V2 residues and the glycan-N160. Two prototype bnAbs were derived from VH-germlines that were 99% identical and used a common germline D-gene encoded YYD-motif to interact with the V2-epitope. We identified isolates that were neutralized by inferred germline (iGL) versions of three of the prototype bnAbs. Soluble Env derived from one of these isolates was shown to form a well-ordered Env trimer that could serve as an immunogen to initiate a V2-apex bnAb response. These studies illustrate a strategy to transition from panels of bnAbs to vaccine candidates.

Publication types

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

MeSH terms

Amino Acid Sequence
Antibodies, Neutralizing / immunology*
Epitopes / immunology
HEK293 Cells
HIV Antibodies / immunology*
HIV Infections / immunology
HIV-1 / immunology*
Humans
Molecular Sequence Data
Vaccines / immunology*
Viral Envelope Proteins / immunology*
env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

Antibodies, Neutralizing
Epitopes
HIV Antibodies
Vaccines
Viral Envelope Proteins
env Gene Products, Human Immunodeficiency Virus

Associated data

GENBANK/KT252544
GENBANK/KT252545

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding