title: Immunization with an SIV-based IDLV Expressing HIV-1 Env 1086 Clade C Elicits Durable Humoral and Cellular Responses in Rhesus Macaques.
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.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA; Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Negri
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Blasi
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Celia
authors.initials: C
authors.lastname: LaBranche
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Parks
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Harikrishnan
authors.initials: H
authors.lastname: Balachandran
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lifton
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Denny
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Maria Fenicia
authors.initials: MF
authors.lastname: Vescio
authors.affiliation: BIOQUAL Inc., Rockville, Maryland, USA.
authors.forename: Hanne
authors.initials: H
authors.lastname: Andersen
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Sampa
authors.initials: S
authors.lastname: Santra
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA. Electronic address: mary.klotman@dm.duke.edu.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Klotman
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA; Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy. Electronic address: andrea.cara1@duke.edu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cara
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D019426:Integrases / Q000172:deficiency*; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism; D014611:Vaccination / Q000379:methods; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D054299:env Gene Products, Human Immunodeficiency Virus; D019426:Integrases