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J Immunol ; 190(8): 4103-15, 2013 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-23509365

RESUMO

Prime-boost immunization with heterologous vaccines elicits potent cellular immunity. In this study, we assessed the influence of various TLR ligands on SIV Gag-specific T cell immunity and protection following prime-boost immunization. Rhesus macaques (RMs) were primed with SIV Gag protein emulsified in Montanide ISA51 with or without TLR3 (polyinosinic-polycytidylic acid [poly-IC]), TLR4 (monophosphoryl lipid A), TLR7/8 (3M-012), TLR9 (CpG), or TLR3 (poly-IC) combined with TLR7/8 ligands, then boosted with replication defective adenovirus 5 expressing SIV Gag (rAd5-Gag). After priming, RMs that received SIV Gag protein plus poly-IC developed significantly higher frequencies of SIV Gag-specific CD4(+) Th1 responses in blood and bronchoalveolar lavage (BAL) fluid lymphocytes compared with all other adjuvants, and low-level SIV Gag-specific CD8(+) T cell responses. After the rAd5-Gag boost, the magnitude and breadth of SIV Gag-specific CD8(+) T cell responses were significantly increased in RM primed with SIV Gag protein plus poly-IC, with or without the TLR7/8 ligand, or CpG. However, the anamnestic, SIV Gag-specific CD8(+) T cell response to SIVmac251 challenge was not significantly enhanced by SIV Gag protein priming with any of the adjuvants. In contrast, the anamnestic SIV Gag-specific CD4(+) T cell response in BAL was enhanced by SIV Gag protein priming with poly-IC or CpG, which correlated with partial control of early viral replication after SIVmac251 challenge. These results demonstrate that prime-boost vaccination with SIV Gag protein/poly-IC improves magnitude, breadth, and durability of CD4(+) T cell immune responses, which could have a role in the control of SIV viral replication.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Produtos do Gene gag/administração & dosagem , Poli I-C/administração & dosagem , Receptores de Antígenos de Linfócitos T/fisiologia , Subpopulações de Linfócitos T/imunologia , Adjuvantes Imunológicos/uso terapêutico , Animais , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/metabolismo , Produtos do Gene gag/imunologia , Macaca mulatta , Manitol/administração & dosagem , Manitol/análogos & derivados , Manitol/uso terapêutico , Ácidos Oleicos/administração & dosagem , Ácidos Oleicos/uso terapêutico , Poli I-C/uso terapêutico , Vírus da Imunodeficiência Símia/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/virologia
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