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Adenovirally-Induced Polyfunctional T Cells Do Not Necessarily Recognize the Infected Target: Lessons from a Phase I Trial of the AERAS-402 Vaccine.
Nyendak, Melissa; Swarbrick, Gwendolyn M; Duncan, Amanda; Cansler, Meghan; Huff, Ervina Winata; Hokey, David; Evans, Tom; Barker, Lewellys; Blatner, Gretta; Sadoff, Jerald; Douoguih, Macaya; Pau, Maria Grazia; Lewinsohn, Deborah A; Lewinsohn, David M.
Afiliación
  • Nyendak M; Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA.
  • Swarbrick GM; Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.
  • Duncan A; Department of Medicine, Portland VA Medical Center, Portland, Oregon, USA.
  • Cansler M; Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.
  • Huff EW; Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.
  • Hokey D; Department of Medicine, Portland VA Medical Center, Portland, Oregon, USA.
  • Evans T; Aeras, Rockville, Maryland, USA.
  • Barker L; Aeras, Rockville, Maryland, USA.
  • Blatner G; Aeras, Rockville, Maryland, USA.
  • Sadoff J; Aeras, Rockville, Maryland, USA.
  • Douoguih M; Janssen Infectious Diseases and Vaccines (formerly Crucell), Leiden, The Netherlands.
  • Pau MG; Janssen Infectious Diseases and Vaccines (formerly Crucell), Leiden, The Netherlands.
  • Lewinsohn DA; Janssen Infectious Diseases and Vaccines (formerly Crucell), Leiden, The Netherlands.
  • Lewinsohn DM; Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.
Sci Rep ; 6: 36355, 2016 11 02.
Article en En | MEDLINE | ID: mdl-27805026
The development of a vaccine for Mycobacterium tuberculosis (Mtb) has been impeded by the absence of correlates of protective immunity. One correlate would be the ability of cells induced by vaccination to recognize the Mtb-infected cell. AERAS-402 is a replication-deficient serotype 35 adenovirus containing DNA expressing a fusion protein of Mtb antigens 85A, 85B and TB10.4. We undertook a phase I double-blind, randomized placebo controlled trial of vaccination with AERAS-402 following BCG. Analysis of the vaccine-induced immune response revealed strong antigen-specific polyfunctional CD4+ and CD8+ T cell responses. However, analysis of the vaccine-induced CD8+ T cells revealed that in many instances these cells did not recognize the Mtb-infected cell. Our findings highlight the measurement of vaccine-induced, polyfunctional T cells may not reflect the extent or degree to which these cells are capable of identifying the Mtb-infected cell and correspondingly, the value of detailed experimental medicine studies early in vaccine development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD4-Positivos / Linfocitos T CD8-positivos / Vacunas contra la Tuberculosis / Mycobacterium tuberculosis Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Female / Humans / Male Idioma: En Revista: Sci Rep Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD4-Positivos / Linfocitos T CD8-positivos / Vacunas contra la Tuberculosis / Mycobacterium tuberculosis Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Female / Humans / Male Idioma: En Revista: Sci Rep Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido