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

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 give...

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Published in:Molecular therapy 2016-11, Vol.24 (11), p.2021-2032
Main Authors: Negri, Donatella, Blasi, Maria, LaBranche, Celia, Parks, Robert, Balachandran, Harikrishnan, Lifton, Michelle, Shen, Xiaoying, Denny, Thomas, Ferrari, Guido, Vescio, Maria Fenicia, Andersen, Hanne, Montefiori, David C, Tomaras, Georgia D, Liao, Hua-Xin, Santra, Sampa, Haynes, Barton F, Klotman, Mary E, Cara, Andrea
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
AIDS Vaccines - administration & dosage
AIDS Vaccines - immunology
Animals
Antibodies
Antigens
Cell division
Cytotoxicity
env Gene Products, Human Immunodeficiency Virus - genetics
env Gene Products, Human Immunodeficiency Virus - immunology
Immunity, Cellular
Immunization
Immunization, Secondary
Infectious diseases
Injections, Intramuscular
Integrases - deficiency
Lentivirus
Macaca mulatta
Monkeys & apes
Original
Plasma
Proteins
Simian Immunodeficiency Virus - genetics
T-Lymphocytes - metabolism
Vaccination - methods
Vaccines
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Summary: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.
ISSN:1525-0016
1525-0024
DOI:10.1038/mt.2016.123