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- W1580360668 abstract "Replication-defective adenoviral vectors based on human serotype 5 (H5) have emerged as very effective vaccine carriers. However, the neutralizing antibodies to AdH5 vector by previous natural infections will very likely impair its vaccine efficacy. Therefore, our lab developed replication-defective simian adenoviral C7 vectors to circumvent interference by pre-existing immunity to human AdH5. Early regions of AdH5 genome, including E1, E3, and E4, have been suggested to influence persistence of transgene expression and vector toxicity in mice. Therefore, we used Ebola Zaire virus envelope glycoprotein (Ebo GP) as a model antigen to create a panel of C7 vaccine vectors, including C7.000CMVGP with a deletion in E1 region, C7.010CMVGP with deletions in both E1 and E3 regions, and C7.001CMVGP with deletions in both E1 and E4 regions. The transgene expression cassette was incorporated into E1 regions of these vectors. By western blot analysis, C7.000CMVGP and C7.010CMVGP vectors yielded very similar level of GP expression, while C7.001CMVGP vector produced significantly less GP protein in transduced A549 cells. By intracellular cytokine staining with H-2k restricted GP-specific peptide as stimulant, similar frequencies of CD8+ T cells producing IFN-g were observed in B10BR mice vaccinated with C7.000CMVGP or C7.001CMVGP, while slightly higher frequencies of CD8+ T cells producing IFN-g were observed in B10BR mice vaccinated with C7.010CMVGP. Total IgG responses to GP, measured by ELISA, were equivalent in serum from vaccinated mice with either of these vectors. We are currently investigating whether a single administration of either of these vectors can protect mice against lethal challenge of a mouse-adapted strain of Ebola Zaire virus. Ongoing study also indicated that better GP-specific T cell and B cell responses can be achieved by priming with either C7.010CMVGP or C7.001CMVGP and boosting with H5CMVGP than by priming with C7.000CMVGP and boosting with H5CMVGP. Overall, these data suggested that multi-defective simian adenoviral vectors may be better vaccine carriers." @default.
- W1580360668 created "2016-06-24" @default.
- W1580360668 date "2004-05-01" @default.
- W1580360668 modified "2023-09-24" @default.
- W1580360668 title "Comparison of Antigen-Specific Immune Responses Elicited by Recombinant Simian Adenoviral Vectors with Deletions in Either E1, or E1/E3, or E1/E4 Regions" @default.
- W1580360668 doi "https://doi.org/10.1016/j.ymthe.2004.06.491" @default.
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