Antigenicity and immunogenicity of a trimeric envelope protein from an Indian clade C HIV-1 isolate.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Sneha Priya, R; Veena, M; Kalisz, I; Whitney, S; Priyanka, D; LaBranche, CC; Sri Teja, M; Montefiori, DC; Pal, R; Mahalingam, S; Kalyanaraman, VS

Published Date

  • April 3, 2015

Published In

Volume / Issue

  • 290 / 14

Start / End Page

  • 9195 - 9208

PubMed ID

  • 25691567

Pubmed Central ID

  • 25691567

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.M114.621185

Language

  • eng

Conference Location

  • United States