title: The Thai phase III trial (RV144) vaccine regimen induces T cell responses that preferentially target epitopes within the V2 region of HIV-1 envelope.
abstract: The Thai HIV phase III prime/boost vaccine trial (RV144) using ALVAC-HIV (vCP1521) and AIDSVAX B/E was, to our knowledge, the first to demonstrate acquisition efficacy. Vaccine-induced, cell-mediated immune responses were assessed. T cell epitope mapping studies using IFN-γ ELISPOT was performed on PBMCs from HIV-1-uninfected vaccine (n = 61) and placebo (n = 10) recipients using HIV-1 Env peptides. Positive responses were measured in 25 (41%) vaccinees and were predominantly CD4(+) T cell-mediated. Responses were targeted within the HIV Env region, with 15 of 25 (60%) of vaccinees recognizing peptides derived from the V2 region of HIV-1 Env, which includes the α(4)β(7) integrin binding site. Intracellular cytokine staining confirmed that Env responses predominated (19 of 30; 63% of vaccine recipients) and were mediated by polyfunctional effector memory CD4(+) T cells, with the majority of responders producing both IL-2 and IFN-γ (12 of 19; 63%). HIV Env Ab titers were higher in subjects with IL-2 compared with those without IL-2-secreting HIV Env-specific effector memory T cells. Proliferation assays revealed that HIV Ag-specific T cells were CD4(+), with the majority (80%) expressing CD107a. HIV-specific T cell lines obtained from vaccine recipients confirmed V2 specificity, polyfunctionality, and functional cytolytic capacity. Although the RV144 T cell responses were modest in frequency compared with humoral immune responses, the CD4(+) T cell response was directed to HIV-1 Env and more particularly the V2 region.
authors.affiliation: U.S. Military HIV Research Program/U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand. desouzams@afrims.org
authors.forename: Mark S
authors.initials: MS
authors.lastname: de Souza
authors.forename: Silvia
authors.initials: S
authors.lastname: Ratto-Kim
authors.forename: Weerawan
authors.initials: W
authors.lastname: Chuenarom
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schuetz
authors.forename: Somsak
authors.initials: S
authors.lastname: Chantakulkij
authors.forename: Bessara
authors.initials: B
authors.lastname: Nuntapinit
authors.forename: Anais
authors.initials: A
authors.lastname: Valencia-Micolta
authors.forename: Doris
authors.initials: D
authors.lastname: Thelian
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.forename: Robert M
authors.initials: RM
authors.lastname: Paris
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkungwal
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: Supachai
authors.initials: S
authors.lastname: Rerks-Ngarm
authors.forename: Bonnie
authors.initials: B
authors.lastname: Mathieson
authors.forename: Mary
authors.initials: M
authors.lastname: Marovich
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Currier
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000595:Amino Acid Sequence; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D015483:HIV Antibodies / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D052118:Lysosomal-Associated Membrane Protein 1