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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Carnathan, Diane G. Wetzel, Katherine S. Ertl, Hildegund C. J. Johnson, Brent A. Yan, Jian Lee, S. Thera Yu, Joana Morrow, Matthew P. Paiardini, Mirko Weiner, David B. Sardesai, Niranjan Y. Silvestri, Guido |
| Description | Author Affiliation: Carnathan DG ( Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329); Wetzel KS ( Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329); Yu J ( Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329); Lee ST ( Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329); Johnson BA ( Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY 14642); Paiardini M ( Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329); Yan J ( Inovio Pharmaceuticals, Plymouth Meeting, PA 19462); Morrow MP ( Inovio Pharmaceuticals, Plymouth Meeting, PA 19462); Sardesai NY ( Inovio Pharmaceuticals, Plymouth Meeting, PA 19462); Weiner DB ( Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104); Ertl HC ( Wistar Institute, Philadelphia, PA 19104.); Silvestri G ( Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329); |
| Abstract | An effective T-cell-based AIDS vaccine should induce strong HIV-specific CD8(+) T cells in mucosal tissues without increasing the availability of target cells for the virus. Here, we evaluated five immunization strategies that include Human adenovirus-5 (AdHu5), Chimpanzee adenovirus-6 (AdC6) or -7 (AdC7), Vaccinia virus (VV), and DNA given by electroporation (DNA/EP), all expressing Simian immunodeficiency virus group specific antigen/transactivator of transcription (SIV(mac239Gag/Tat)). Five groups of six rhesus macaques (RMs) each were vaccinated with DNA/EP-AdC6-AdC7, VV-AdC6-AdC7, DNA/-EP-VV-AdC6, DNA/EP-VV-AdC7, or AdHu5-AdHu5-AdHu5 and were challenged repeatedly with low-dose intrarectal SIVmac239. Upon challenge, there were no significant differences among study groups in terms of virus acquisition or viral load after infection. When taken together, the immunization regimens did not protect against SIV acquisition compared with controls but did result in an â ¼ 1.6-log decline in set-point viremia. Although all immunized RMs had detectable SIV-specific CD8(+) T cells in blood and rectal mucosa, we found no correlation between the number or function of these SIV-specific CD8(+) T cells and protection against SIV acquisition. Interestingly, RMs experiencing breakthrough infection showed significantly higher prechallenge levels of CD4(+)C-C chemokine receptor type 5 (CCR5)(+)HLA-DR(+) T cells in the rectal biopsies (RB) than animals that remained uninfected. In addition, among the infected RMs, the percentage of CD4(+)CCR5(+)Ki-67(+) T cells in RBs prechallenge correlated with higher early viremia. Overall, these data suggest that the levels of activated CD4(+)CCR5(+) target T cells in the rectal mucosa may predict the risk of SIV acquisition in RMs vaccinated with vectors that express SIVGag/Tat. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 2 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | CD4-Positive T-Lymphocytes Immunology Virology SAIDS Vaccines Simian Immunodeficiency Virus T-Lymphocyte Subsets Animals CD8-Positive T-Lymphocytes Gene Products, Gag Gene Products, Tat Immunity, Cellular Immunity, Mucosal Lymphocyte Activation Macaca Mulatta Receptors, CCR5 Metabolism Simian Acquired Immunodeficiency Syndrome Prevention & Control Pathogenicity Vaccination Viremia Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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