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de Souza, Mark S.; Ratto-Kim, Silvia; Chuenarom, Weerawan; Schuetz, Alexandra; Chantakulkij, Somsak; Nuntapinit, Bessara; Valencia-Micolta, Anais; Thelian, Doris; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Paris, Robert M.; Kaewkungwal, Jaranit; Michael, Nelson L.; Rerks-Ngarm, Supachai; Mathieson, Bonnie; Marovich, Mary; Currier, Jeffrey R.; Kim, Jerome H.; Rerks-Ngarm, Supachai; Chunsuttiwat, Supamit; Premsri, Nakorn; Namwat, Chawetsan; Kunasol, Prayura; Thongcharoen, Prasert; [...]

The Thai Phase III Trial (RV144) Vaccine Regimen Induces T Cell Responses That Preferentially Target Epitopes within the V2 Region of HIV-1 Envelope

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  • Medientyp: E-Artikel
  • Titel: The Thai Phase III Trial (RV144) Vaccine Regimen Induces T Cell Responses That Preferentially Target Epitopes within the V2 Region of HIV-1 Envelope
  • Beteiligte: de Souza, Mark S.; Ratto-Kim, Silvia; Chuenarom, Weerawan; Schuetz, Alexandra; Chantakulkij, Somsak; Nuntapinit, Bessara; Valencia-Micolta, Anais; Thelian, Doris; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Paris, Robert M.; Kaewkungwal, Jaranit; Michael, Nelson L.; Rerks-Ngarm, Supachai; Mathieson, Bonnie; Marovich, Mary; Currier, Jeffrey R.; Kim, Jerome H.; Rerks-Ngarm, Supachai; Chunsuttiwat, Supamit; Premsri, Nakorn; Namwat, Chawetsan; Kunasol, Prayura; Thongcharoen, Prasert; [...]
  • Erschienen: The American Association of Immunologists, 2012
  • Erschienen in: The Journal of Immunology, 188 (2012) 10, Seite 5166-5176
  • Sprache: Englisch
  • DOI: 10.4049/jimmunol.1102756
  • ISSN: 0022-1767; 1550-6606
  • Entstehung:
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  • Beschreibung: 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 α4β7 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.
  • Zugangsstatus: Freier Zugang