title: Neutralization resistant HIV-1 primary isolates from antiretroviral naïve chronically infected children in India.
abstract: Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been extensively tested against pesudoviruses of diverse strains. We generated and characterized HIV-1 primary isolates from antiretroviral naïve infected Indian children, and determined their susceptibility to known NAbs. All the 8 isolates belonged to subtype-C and were R5 tropic. Majority of these viruses were resistant to neutralization by NAbs, suggesting that the bnAbs, known to efficiently neutralize pseudoviruses (adult and pediatric) of different strains, are less effective against pediatric primary isolates. Interestingly, AIIMS_329 isolate displayed high susceptibility to neutralization by PG9 and PG16bnAbs, with IC50titer of 1.3 and 0.97μg/ml, suggesting exposure of this epitope on this virus. All isolates except AIIMS_506 were neutralized by contemporaneous plasma antibodies. Our findings suggest that primary isolates, due to close resemblance to viruses in natural infection, should be used to evaluate NAbs as effective vaccine candidates in both children and adults.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Muzamil Ashraf
authors.initials: MA
authors.lastname: Makhdoomi
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Deepti
authors.initials: D
authors.lastname: Singh
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India; Department of Biochemistry, Jamia Hamdard University, 110062 New Delhi, India.
authors.forename: Ambili
authors.initials: A
authors.lastname: Nair Pananghat
authors.affiliation: Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Lodha
authors.affiliation: Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Sushil Kumar
authors.initials: SK
authors.lastname: Kabra
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: kalpanaluthra@gmail.com.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Luthra
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000276:immunology; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D000939:Epitopes / Q000276:immunology; D005260:Female; D005838:Genotype; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D010802:Phylogeny; D011485:Protein Binding; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D019562:Viral Load
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4
keywords: AMD3100; Broadly neutralizing antibodies; CCR5, CXCR4; Contemporaneous plasma; Neutralization resistant; Pediatric HIV-1 isolates; TAK779