title: Determinants in V2C2 region of HIV-1 clade C primary envelopes conferred altered neutralization susceptibilities to IgG1b12 and PG9 monoclonal antibodies in a context-dependent manner.
abstract: In the present study by examining pseudoviruses expressing patient chimeric envelopes (Envs) made between an IgG1b12 (b12)-sensitive (2-5.J3) and a b12-resistant (4.J22) HIV-1 clade C envelope, we identified determinants in the V2C2 region that governed susceptibility to b12 monoclonal antibody, but not to other CD4 binding site antibodies. Interestingly, when the V2C2 sequence of the 2-5.J3 Env was transferred to other b12-resistant primary clade C Envs, their susceptibility to b12 varied, indicating that this effect was context dependent. In addition, we identified determinants within the V2 region in the b12-resistant envelope that significantly modulated the neutralization of Env-pseudotyped viruses to PG9/PG16 MAbs. The enhanced neutralization susceptibilities of Envs to b12 and PG9 MAbs were correlated with increased exposure of their corresponding epitopes highlighting vulnerabilities in the V2C2 region that altered Env conformation necessary for the efficient accessibility of b12 and PG9 antibodies.
authors.affiliation: HIV Vaccine Translational Research Laboratory, THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 450, Udyog Vihar, Phase-III, Gurgaon 122016, Haryana, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Patil
authors.affiliation: National AIDS Research Institute, Pune, Maharashtra, India.
authors.forename: Ipsita
authors.initials: I
authors.lastname: Choudhary
authors.affiliation: HIV Vaccine Translational Research Laboratory, THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 450, Udyog Vihar, Phase-III, Gurgaon 122016, Haryana, India.
authors.forename: Nakul K
authors.initials: NK
authors.lastname: Chaudhary
authors.affiliation: National AIDS Research Institute, Pune, Maharashtra, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ringe
authors.affiliation: HIV Vaccine Translational Research Laboratory, THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 450, Udyog Vihar, Phase-III, Gurgaon 122016, Haryana, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Bansal
authors.affiliation: HIV Vaccine Translational Research Laboratory, THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 450, Udyog Vihar, Phase-III, Gurgaon 122016, Haryana, India.
authors.forename: Brihaspati Narayan
authors.initials: BN
authors.lastname: Shukla
authors.affiliation: HIV Vaccine Translational Research Laboratory, THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 450, Udyog Vihar, Phase-III, Gurgaon 122016, Haryana, India.
authors.forename: Saikat
authors.initials: S
authors.lastname: Boliar
authors.affiliation: HIV Vaccine Translational Research Laboratory, THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 450, Udyog Vihar, Phase-III, Gurgaon 122016, Haryana, India.
authors.forename: Bimal K
authors.initials: BK
authors.lastname: Chakrabarti
authors.affiliation: HIV Vaccine Translational Research Laboratory, THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 450, Udyog Vihar, Phase-III, Gurgaon 122016, Haryana, India. Electronic address: JBhattacharya@iavi.org.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Bhattacharya
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology*; D005838:Genotype; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D018985:Epitopes, B-Lymphocyte; D015686:Gene Products, env; D015483:HIV Antibodies
keywords: CD4bs; Clade C; Envelope; HIV-1; IgG1b12; Neutralizing antibody; PG16; PG9; VRC01