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Comparison of DNA vaccines producing HIV-1 Gag and LAMP/Gag chimera in rhesus macaques reveals antigen-specific T-cell responses with distinct phenotypes |
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| Authors: | Antonio Valentin Priya Chikhlikar Vainav Patel Margherita Rosati Milton Maciel Kern-Hee Chang Peter Silvera Barbara K. Felber George N. Pavlakis J. Thomas August Ernesto T.A. Marques |
| Affiliation: | 1. Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, P.O. Box B, Building 535, Room 206, Frederick, MD 21702-1201, United States;2. Department of Pharmacology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21210, United States;3. Department of Infectious Diseases, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21210, United States;4. Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, P.O. Box B, Building 535, Room 206, Frederick, MD 21702-1201, United States;5. Southern Research Institute, 431 Aviation Way, Frederick, MD 21701, United States;6. Oswaldo Cruz Foundation (FIOCRUZ), Instituto Aggeu Magalhães, Av. Moraes Rego s/n Campus da Cidade Universitária, Recife PE 50670-420, Brazil |
| Abstract: | Optimized DNA expression vectors encoding the native HIV-1 Gag or a fusion of Gag with the lysosomal membrane associated protein 1 (LAMP) were compared for immunogenicity upon intramuscular DNA delivery in rhesus macaques. Both vaccines elicited CD4+ T-cell responses, but with significant differences in the phenotype of the Gag-specific cells: the native Gag induced CD4+ responses with a phenotype of central memory-like T cells (CD28+ CD45RA−), whereas the LAMP/Gag chimera induced CD4+ responses with effector memory phenotype (CD28− CD45RA−). Antigen-specific T cells producing both IFN-γ and TNFα were found in the animals receiving the native Gag, whereas the LAMP/Gag chimera induced humoral responses faster. These results demonstrate that modification of intracellular Gag trafficking results in the induction of distinct immune responses. Combinations of DNA vectors encoding both forms of antigen may be more potent in eliciting anti-HIV-1 immunity. |
| Keywords: | Central memory Effector memory CD4 CD8 T cells IFN-gamma TNF-alpha IL-2 |
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