Immunization with an SIV-based IDLV Expressing HIV-1 Env 1086 Clade C Elicits Durable Humoral and Cellular Responses in Rhesus Macaques.

Published

Journal Article

The design of an effective HIV-1 vaccine remains a major challenge. Several vaccine strategies based on viral vectors have been evaluated in preclinical and clinical trials, with largely disappointing results. Integrase defective lentiviral vectors (IDLV) represent a promising vaccine candidate given their ability to induce durable and protective immune responses in mice after a single immunization. Here, we evaluated the immunogenicity of a SIV-based IDLV in nonhuman primates. Six rhesus monkeys were primed intramuscularly with IDLV-Env and boosted with the same vector after 1 year. A single immunization with IDLV-Env induced broad humoral and cellular immune responses that waned over time but were still detectable at 1 year postprime. The boost with IDLV-Env performed at 1 year from the prime induced a remarkable increase in both antibodies and T-cell responses. Antibody binding specificity showed a predominant cross-clade gp120-directed response. Monkeys' sera efficiently blocked anti-V2 and anti-CD4 binding site antibodies, neutralized the tier 1 MW965.26 pseudovirus and mediated antibody-dependent cellular cytotoxicity (ADCC). Durable polyfunctional Env-specific T-cell responses were also elicited. Our study demonstrates that an IDLV-Env-based vaccine induces functional, comprehensive, and durable immune responses in Rhesus macaques. These results support further evaluation of IDLV as a new HIV-1 vaccine delivery platform.

Full Text

Duke Authors

Cited Authors

  • Negri, D; Blasi, M; LaBranche, C; Parks, R; Balachandran, H; Lifton, M; Shen, X; Denny, T; Ferrari, G; Vescio, MF; Andersen, H; Montefiori, DC; Tomaras, GD; Liao, H-X; Santra, S; Haynes, BF; Klotman, ME; Cara, A

Published Date

  • November 2016

Published In

Volume / Issue

  • 24 / 11

Start / End Page

  • 2021 - 2032

PubMed ID

  • 27455880

Pubmed Central ID

  • 27455880

Electronic International Standard Serial Number (EISSN)

  • 1525-0024

International Standard Serial Number (ISSN)

  • 1525-0016

Digital Object Identifier (DOI)

  • 10.1038/mt.2016.123

Language

  • eng