High-mannose glycan-dependent epitopes are frequently targeted in broad neutralizing antibody responses during human immunodeficiency virus type 1 infection.
Journal Article (Journal Article)
Broad and potent neutralizing antibody (BNAb) responses are rare in people infected by human immunodeficiency virus type 1 (HIV-1). Clearly defining the nature of BNAb epitopes on HIV-1 envelope glycoproteins (Envs) targeted in vivo is critical for future directions of anti-HIV-1 vaccine development. Conventional techniques are successful in defining neutralizing epitopes in a small number of individual subjects but fail in studying large groups of subjects. Two independent methods were employed to investigate the nature of NAb epitopes targeted in 9 subjects, identified by the NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI) 001 and 008 clinical teams, known to make a strong BNAb response. Neutralizing activity from 8/9 subjects was enhanced by enriching high-mannose N-linked glycan (HM-glycan) of HIV-1 glycoproteins on neutralization target viruses and was sensitive to specific glycan deletion mutations of HIV-1 glycoproteins, indicating that HM-glycan-dependent epitopes are targeted by BNAb responses in these subjects. This discovery adds to accumulating evidence supporting the hypothesis that glycans are important targets on HIV-1 glycoproteins for BNAb responses in vivo, providing an important lead for future directions in developing NAb-based anti-HIV-1 vaccines.
Full Text
Duke Authors
Cited Authors
- Lavine, CL; Lao, S; Montefiori, DC; Haynes, BF; Sodroski, JG; Yang, X; NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI),
Published Date
- February 2012
Published In
Volume / Issue
- 86 / 4
Start / End Page
- 2153 - 2164
PubMed ID
- 22156525
Pubmed Central ID
- 22156525
Electronic International Standard Serial Number (EISSN)
- 1098-5514
Digital Object Identifier (DOI)
- 10.1128/JVI.06201-11
Language
- eng
Conference Location
- United States