title: An efficiently cleaved HIV-1 clade C Env selectively binds to neutralizing antibodies.
abstract: An ideal HIV-1 Env immunogen is expected to mimic the native trimeric conformation for inducing broadly neutralizing antibody responses. The native conformation is dependent on efficient cleavage of HIV-1 Env. The clade B isolate, JRFL Env is efficiently cleaved when expressed on the cell surface. Here, for the first time, we report the identification of a native clade C Env, 4-2.J41 that is naturally and efficiently cleaved on the cell surface as confirmed by its biochemical and antigenic characteristics. In addition to binding to several conformation-dependent neutralizing antibodies, 4-2.J41 Env binds efficiently to the cleavage-dependent antibody PGT151; thus validating its native cleaved conformation. In contrast, 4-2.J41 Env occludes non-neutralizing epitopes. The cytoplasmic-tail of 4-2.J41 Env plays an important role in maintaining its conformation. Furthermore, codon optimization of 4-2.J41 Env sequence significantly increases its expression while retaining its native conformation. Since clade C of HIV-1 is the prevalent subtype, identification and characterization of this efficiently cleaved Env would provide a platform for rational immunogen design.
authors.affiliation: THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 496 Udyog Vihar, Phase-III, Gurgaon-122 016, Haryana, India.
authors.forename: Saikat
authors.initials: S
authors.lastname: Boliar
authors.affiliation: THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 496 Udyog Vihar, Phase-III, Gurgaon-122 016, Haryana, India.
authors.forename: Supratik
authors.initials: S
authors.lastname: Das
authors.affiliation: THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 496 Udyog Vihar, Phase-III, Gurgaon-122 016, Haryana, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Bansal
authors.affiliation: THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 496 Udyog Vihar, Phase-III, Gurgaon-122 016, Haryana, India.
authors.forename: Brihaspati N
authors.initials: BN
authors.lastname: Shukla
authors.affiliation: THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 496 Udyog Vihar, Phase-III, Gurgaon-122 016, Haryana, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Patil
authors.affiliation: THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 496 Udyog Vihar, Phase-III, Gurgaon-122 016, Haryana, India.
authors.forename: Tripti
authors.initials: T
authors.lastname: Shrivastava
authors.affiliation: THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 496 Udyog Vihar, Phase-III, Gurgaon-122 016, Haryana, India.
authors.forename: Sweety
authors.initials: S
authors.lastname: Samal
authors.affiliation: THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 496 Udyog Vihar, Phase-III, Gurgaon-122 016, Haryana, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Goswami
authors.affiliation: IAVI Vaccine Design, New York, NY, United States of America.
authors.forename: C Richter
authors.initials: CR
authors.lastname: King
authors.affiliation: THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 496 Udyog Vihar, Phase-III, Gurgaon-122 016, Haryana, India.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Bhattacharya
authors.affiliation: THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 496 Udyog Vihar, Phase-III, Gurgaon-122 016, Haryana, India.
authors.forename: Bimal K
authors.initials: BK
authors.lastname: Chakrabarti
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000918:Antibody Specificity; D015704:CD4 Antigens / Q000737:chemistry / Q000494:pharmacology; D003062:Codon / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009154:Mutation; D011487:Protein Conformation; D059748:Proteolysis; D012995:Solubility; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D003062:Codon; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D054299:env Gene Products, Human Immunodeficiency Virus
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