title: Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual.
abstract: Dissecting antibody specificities in the plasma of HIV-1 infected individuals that develop broadly neutralizing antibodies (bNAbs) is likely to provide useful information for refining target epitopes for vaccine design. Several studies have reported CD4-binding site (CD4bs) antibodies as neutralization determinants in the plasma of subtype B-infected individuals; however there is little information on the prevalence of CD4bs specificities in HIV-infected individuals in India. Here, we report on the presence of CD4bs antibodies and their contribution to virus neutralization in the plasma from a cohort of HIV-1 infected Indian individuals. Plasma from 11 of the 140 HIV-1 infected individuals (7.9%) studied here exhibited cross-neutralization activity against a panel of subtype B and C viruses. Analyses of these 11 plasma samples for the presence of CD4bs antibodies using two CD4bs-selective probes (antigenically resurfaced HXB2gp120 core protein RSC3 and hyperglycosylated JRFLgp120 mutant ΔN2mCHO) revealed that five (AIIMS 617, 619, 627, 642, 660) contained RSC3-reactive plasma antibodies and only one (AIIMS 660) contained ΔN2mCHO-reactive antibodies. Plasma antibody depletion and competition experiments confirmed that the neutralizing activity in the AIIMS 660 plasma was dependent on CD4bs antibodies. To the best of our knowledge, this is the first study to report specifically on the presence of CD4bs antibodies in the plasma of a cohort of HIV-1 infected Indian donors. The identification of CD4bs dependent neutralizing antibodies in an HIV-1 infected Indian donor is a salient finding of this study and is supportive of ongoing efforts to induce similar antibodies by immunization.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Lubina
authors.initials: L
authors.lastname: Khan
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Muzamil Ashraf
authors.initials: MA
authors.lastname: Makhdoomi
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ambili
authors.initials: A
authors.lastname: Nair
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Raiees
authors.initials: R
authors.lastname: Andrabi
authors.affiliation: Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Brenda E
authors.initials: BE
authors.lastname: Clark
authors.affiliation: Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Kate
authors.initials: K
authors.lastname: Auyeung
authors.affiliation: HIV Vaccine Translational Research Laboratory, THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, Gurgaon, Haryana, India.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Bhattacharya
authors.affiliation: Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Madhu
authors.initials: M
authors.lastname: Vajpayee
authors.affiliation: Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Naveet
authors.initials: N
authors.lastname: Wig
authors.affiliation: Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Ralph
authors.initials: R
authors.lastname: Pantophlet
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Luthra
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology*; D001666:Binding Sites, Antibody; D015704:CD4 Antigens / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D015483:HIV Antibodies