1. ¹Animal Models and Retroviral Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
2. ²Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
3. ³California National Primate Research Center, University of California, Davis, California, USA
4. ⁴Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
5. ⁵Division of Biological Chemistry Biocentre, Innsbruck Medical University, Innsbruck, Austria
6. ⁶Human Retrovirus Pathogenesis Section, NCI-Frederick, National Institutes of Health, Frederick, Maryland, USA
7. ⁷Human Retrovirus Section, NCI-Frederick, National Institutes of Health, Frederick, Maryland, USA

Correspondence: G Franchini, (franchig@mail.nih.gov)

⁸Present address: Department of Immunology, Faculty of Medicine, Imperial College, Chelsea and Westminster Hospital, London, UK.

Received 19 May 2008; Accepted 8 August 2008; Published online 17 September 2008.

Abstract

Systemic immunization of macaques with a combination of DNA-poxvirus-based vaccines confers protection from high level of both systemic and mucosal viral replication following rectal exposure to the pathogenic SIV_mac251. Here we investigated early post-infection events in rectal and vaginal tissues, and found that the loss of CCR5⁺CD4⁺ T cells was equivalent in vaccinated and control macaques, despite a three logs reduction at mucosal sites of simian immunodeficiency virus (SIV) RNA in the vaccinated group. Even though a normal CD4⁺ T cell number is not reconstituted at mucosal sites in either group, vaccination appeared to confer a better preservation of the CD4⁺ CCR5⁺ T cells that replenish these sites. Analysis of rectal tissues RNA following challenge exposure demonstrated a decreased expression in vaccinated macaques of transforming growth factor-, cytotoxic T lymphocyte antigen-4, FoxP3, and indoleamine 2,3-dioxygenase, an immune suppressive enzyme expressed by dendritic cells that converts tryptophan to kynurenine and limits T-cell responses. Accordingly, the ratio of kynurenine and tryptophan in the plasma was significantly reduced in the vaccinated animals respect to the controls. Thus, preexisting adaptive immune responses induced by these vaccine modalities, although they do not protect from CD4⁺ T-cell depletion, nevertheless, they contain SIV_mac251 replication and delay expression of markers of T-cell activation and/or suppression at mucosal sites.