Journal
VIROLOGY
Volume 382, Issue 2, Pages 226-238Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2008.09.019
Keywords
Vaccine; Adjuvant; Interferon-beta; Rabies
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Funding
- NIH/NIAID [R01 A1049153]
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Type I interferon is important in anti-viral responses and in coordinating the innate immune response. Here we explore the use of interferon-beta to adjuvant the response to a rabies virus (RV) vaccine vector expressing both HIV-1 Gag and IFN-beta. Viral load and immune responses of immunized mice were analyzed Over time. Our results indicate that the RV expressing IFN-beta (IFN(+)) is highly attenuated when compared to control RV and demonstrate that the expression of IFN-beta reduces Viral replication approximately 100-fold. Despite the decrease in replication, those mice immunized with the IFN(+) RV had a significantly greater number Of activated CD8+ T cells. The increased activation of CD8+ T cells was dependent oil IFN-beta signaling, as we saw no difference following infection of IFNAR-/- mice. Although mice immunized with IFN(+) have a greater primary immune response than controls, immunized mice that were challenged with vaccinia-expressing Gag had no significant difference in the number or functionality of CD8+ T cells. The increased CD8+ T cell activation in the presence of IFN-beta even with greatly reduced viral replication, indicates the beneficial effect of IFN-beta for the host. (C) 2008 Elsevier Inc. All Fights reserved.
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