title: High-mannose glycan-dependent epitopes are frequently targeted in broad neutralizing antibody responses during human immunodeficiency virus type 1 infection.
abstract: 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.
authors.affiliation: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Christy L
authors.initials: CL
authors.lastname: Lavine
authors.forename: Socheata
authors.initials: S
authors.lastname: Lao
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Sodroski
authors.forename: Xinzhen
authors.initials: X
authors.lastname: Yang
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008358:Mannose / Q000276:immunology*; D009500:Neutralization Tests; D011134:Polysaccharides / Q000235:genetics / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D011134:Polysaccharides; D054299:env Gene Products, Human Immunodeficiency Virus; D008358:Mannose