Nonneutralizing Antibodies Induced by the HIV-1 gp41 NHR Domain Gain Neutralizing Activity in the Presence of the HIV Fusion Inhibitor Enfuvirtide: a Potential Therapeutic Vaccine Strategy

Qian Wang; Wenwen Bi; Xiaojie Zhu; Haoyang Li; Qianqian Qi; Fei Yu; Lu Lu; Shibo Jiang

doi:10.1128/JVI.00791-15

Nonneutralizing Antibodies Induced by the HIV-1 gp41 NHR Domain Gain Neutralizing Activity in the Presence of the HIV Fusion Inhibitor Enfuvirtide: a Potential Therapeutic Vaccine Strategy

J Virol. 2015 Jul;89(13):6960-4. doi: 10.1128/JVI.00791-15. Epub 2015 Apr 22.

Authors

Qian Wang¹, Wenwen Bi¹, Xiaojie Zhu¹, Haoyang Li¹, Qianqian Qi², Fei Yu¹, Lu Lu³, Shibo Jiang⁴

Affiliations

¹ Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
² Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.
³ Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China lul@fudan.edu.cn shibojiang@fudan.edu.cn.
⁴ Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA lul@fudan.edu.cn shibojiang@fudan.edu.cn.

Abstract

A key barrier against developing preventive and therapeutic human immunodeficiency virus (HIV) vaccines is the inability of viral envelope glycoproteins to elicit broad and potent neutralizing antibodies. However, in the presence of fusion inhibitor enfuvirtide, we show that the nonneutralizing antibodies induced by the HIV type 1 (HIV-1) gp41 N-terminal heptad repeat (NHR) domain (N63) exhibit potent and broad neutralizing activity against laboratory-adapted HIV-1 strains, including the drug-resistant variants, and primary HIV-1 isolates with different subtypes, suggesting the potential of developing gp41-targeted HIV therapeutic vaccines.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing / immunology*
Enfuvirtide
HIV Antibodies / immunology*
HIV Envelope Protein gp41 / immunology*
HIV Envelope Protein gp41 / pharmacology*
HIV Fusion Inhibitors / pharmacology*
HIV-1 / drug effects*
HIV-1 / immunology*
Humans
Mice
Neutralization Tests
Peptide Fragments / pharmacology*
Rabbits

Substances

Antibodies, Neutralizing
HIV Antibodies
HIV Envelope Protein gp41
HIV Fusion Inhibitors
Peptide Fragments
gp41 protein, Human immunodeficiency virus 1
Enfuvirtide