Effects of MIP-1α, MIP-3α, and MIP-3ß on the Induction of HIV Gag-specific Immune Response with DNA Vaccines.
Mol Ther
; 15(5): 1007-1015, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-28182892
ABSTRACT
Transfection of DNA vaccines with chemokines may recruit dendritic cells (DCs) locally to capture the antigenic genes and their gene products to generate enhanced CD8+ cytotoxic T lymphocytes (CTLs). In this study, we investigated the effects of macrophage inflammatory protein (MIP)-1α, MIP-3α, and MIP-3ß on human immunodeficiency virus (HIV) Gag DNA vaccination. The chemokine plasmids markedly enhanced the local infiltration of inflammatory cells and increased the presence of CD11c+ B7.2+-activated DCs. MIP-1α and MIP-3α were potent adjuvants in augmenting CTLs and afforded strong protection to immunized animals against challenge with vaccinia virus expressing Gag (vv-Gag). However, decreased humoral response was observed. MIP-3ß plasmid did not dramatically alter immunity. The chemokine inoculation time with respect to DNA vaccine priming was also investigated. The injection of pMIP-3α three days before Gag plasmid (pGag) vaccination markedly increased specific CTLs compared with simultaneous injection and led to higher protection against vv-Gag. Immunity was also shifted toward a T-helper type-1 (Th1) response. In contrast, inoculation with pMIP-3α three days after pGag vaccination shifted immunity toward a Th2 response. Our data suggest that administration of a chemokine with DNA vaccines offers a valuable strategy to modulate the efficacy and polarization of specific immunity and that chemokine-antigen timing is critical in determining overall biological effects.
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Coleções:
01-internacional
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MEDLINE
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En
Ano de publicação:
2007
Tipo de documento:
Article