title: Antigenicity and immunogenicity of a trimeric envelope protein from an Indian clade C HIV-1 isolate.
abstract: Human immunodeficiency virus type 1 (HIV-1) isolates from India mainly belong to clade C and are quite distinct from clade C isolates from Africa in terms of their phylogenetic makeup, serotype, and sensitivity to known human broadly neutralizing monoclonal antibodies. Because many of these properties are associated with the envelope proteins of HIV-1, it is of interest to study the envelope proteins of Indian clade C isolates as part of the ongoing efforts to develop a vaccine against HIV-1. To this end, we purified trimeric uncleaved gp145 of a CCR5 tropic Indian clade C HIV-1 (93IN101) from the conditioned medium of 293 cells. The purified protein was shown to be properly folded with stable structure by circular dichroism. Conformational integrity was further demonstrated by its high affinity binding to soluble CD4, CD4 binding site antibodies such as b12 and VRC01, quaternary epitope-specific antibody PG9, and CD4-induced epitope-specific antibody 17b. Sera from rabbits immunized with gp145 elicited high titer antibodies to various domains of gp120 and neutralized a broad spectrum of clade B and clade C HIV-1 isolates. Similar to other clade B and clade C envelope immunogens, most of the Tier 1 neutralizing activity could be absorbed with the V3-specific peptide. Subsequent boosting of these rabbits with a clade B HIV-1 Bal gp145 resulted in an expanded breadth of neutralization of HIV-1 isolates. The present study strongly supports the inclusion of envelopes from Indian isolates in a future mixture of HIV-1 vaccines.
authors.affiliation: From the Laboratory of Molecular Virology and Cell Biology, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India.
authors.forename: Rangasamy
authors.initials: R
authors.lastname: Sneha Priya
authors.affiliation: Advanced Bioscience Laboratories Inc., Rockville, Maryland 20850, and.
authors.forename: Menon
authors.initials: M
authors.lastname: Veena
authors.affiliation: Advanced Bioscience Laboratories Inc., Rockville, Maryland 20850, and.
authors.forename: Irene
authors.initials: I
authors.lastname: Kalisz
authors.affiliation: Advanced Bioscience Laboratories Inc., Rockville, Maryland 20850, and.
authors.forename: Stephen
authors.initials: S
authors.lastname: Whitney
authors.affiliation: Advanced Bioscience Laboratories Inc., Rockville, Maryland 20850, and.
authors.forename: Dhopeshwarkar
authors.initials: D
authors.lastname: Priyanka
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: Celia C
authors.initials: CC
authors.lastname: LaBranche
authors.affiliation: From the Laboratory of Molecular Virology and Cell Biology, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India.
authors.forename: Mullapudi
authors.initials: M
authors.lastname: Sri Teja
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Advanced Bioscience Laboratories Inc., Rockville, Maryland 20850, and.
authors.forename: Ranajit
authors.initials: R
authors.lastname: Pal
authors.affiliation: From the Laboratory of Molecular Virology and Cell Biology, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India, mahalingam@iitm.ac.in.
authors.forename: Sundarasamy
authors.initials: S
authors.lastname: Mahalingam
authors.affiliation: Advanced Bioscience Laboratories Inc., Rockville, Maryland 20850, and.
authors.forename: Vaniambadi S
authors.initials: VS
authors.lastname: Kalyanaraman
mesh_terms: D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002942:Circular Dichroism; D006224:Cricetinae; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D015488:HIV Antigens; D014759:Viral Envelope Proteins
keywords: AIDS; Antigen; Cell Surface Protein; Human Immunodeficiency Virus (HIV); Vaccine Development