4.6 Article

Systemic and Mucosal T-Lymphocyte Activation Induced by Recombinant Adenovirus Vaccines in Rhesus Monkeys

Journal

JOURNAL OF VIROLOGY
Volume 83, Issue 20, Pages 10596-10604

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01170-09

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Funding

  1. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
  2. Harvard Medical School CFAR [AI060354]
  3. CAVD CTC-VIMC, Bill and Melinda Gates Foundation [38650]

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The administration of vectors designed to elicited cell-mediated immune responses may have other consequences that are clinically significant. To explore this possibility, we evaluated T-cell activation during the first 2 months after recombinant adenovirus serotype 5 (rAd5) prime or boost immunizations in rhesus monkeys. We also evaluated the kinetics of T-lymphocyte activation in both the systemic and the mucosal compartments after rAd5 administration in monkeys with preexisting immunity to Ad5. The rAd5 immunization induced lower-frequency Gag epitope-specific CD8(+) T cells in the colonic mucosa than in the peripheral blood. There was evidence of an expansion of the simian immunodeficiency virus Gag-specific CD8(+) T-cell responses, but not the Ad5 hexon-specific T-cell responses, following a homologous rAd5 boost. A striking but transient T-lymphocyte activation in both the systemic and the mucosal compartments of rhesus monkeys was observed after rAd5 immunization. These findings indicate that the administration of a vaccine vector such as Ad5 can induce a global activation of T cells.

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