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Immunization with an SIV-based IDLV Expressing HIV-1 Env 1086 Clade C Elicits Durable Humoral and Cellular Responses in Rhesus Macaques.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2016 Nov; Vol. 24 (11), pp. 2021-2032. Date of Electronic Publication: 2016 Jun 21. - Publication Year :
- 2016
-
Abstract
- 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.
- Subjects :
- AIDS Vaccines immunology
Animals
Immunity, Cellular
Immunization, Secondary
Injections, Intramuscular
Macaca mulatta
T-Lymphocytes metabolism
Vaccination methods
env Gene Products, Human Immunodeficiency Virus genetics
AIDS Vaccines administration & dosage
Integrases deficiency
Simian Immunodeficiency Virus genetics
env Gene Products, Human Immunodeficiency Virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1525-0024
- Volume :
- 24
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 27455880
- Full Text :
- https://doi.org/10.1038/mt.2016.123