An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge

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• 作者：Natalie A. Hutnick^a ; Devin J.F. Myles^a ; Lauren Hirao^b ; Veronica L. Scott^a ; Bernadette Ferraro^a ; Amir S. Khan^c ; Mark G. Lewis^e ; Christopher J. Miller^f ; Andrew J. Bett^d ; Danilo Casimiro^d ; Niranjan Y. Sardesai^c ; J. Joseph Kim^c ; John Shiver^d ; David B. Weiner^a ; ^{dbweiner@mail.med.upenn.edu}
• 关键词：DNA vaccine ; Adenovirus 5 vaccine ; SIV
• 刊名：Vaccine
• 出版年：2012
• 期刊代码：89_0264410x
• 类别：imm
• 出版时间：2 May, 2012
• 卷：30
• 期：21
• 页码：3202-3208
• 文件大小：480 K

摘要

One limitation in the development of an improved cellular response needed for an effective HIV-vaccine is the inability to induce robust effector T-cells capable of suppressing a heterologous challenge. To improve cellular immune responses, we examined the ability of an optimized DNA vaccine to boost the cellular immune responses induced by a highly immunogenic Ad5 prime. Five Chinese rhesus macaques received pVax encoding consensus (con) gag/pol/env intramuscularly (IM) with electroporation followed by the Merck Ad5 gag/pol/nef vaccine. A second group of five animals were vaccinated with Merck Ad5 gag/pol/nef followed by pVax gag/pol/env. One year following vaccination, Ad5-prime DNA-boosted monkeys and four unvaccinated controls received an intrarectal challenge with 1000 ID50 SIV_mac251. The quality and magnitude of the T-cell response was analyzed by ELISpot and polyfunctional flow cytometry. We observed that an Ad5-prime DNA-boost resulted in significantly elevated SIV-specific T-cell responses even compared with animals receiving a DNA-prime Ad5-boost. Ad5 prime DNA boosted animals were capable of suppressing a pathogenic SIV_mac251 challenge. Peak control correlated with the expansion of HLA-DR⁺ CD8⁺ T-cells two weeks post-infection. These data illustrate that high optimization of a DNA vaccine can drive of immune responses primed by a robust vector system. This previously unachievable feature of these newly optimized DNAs warrants future studies of this strategy that may circumvent issues of serology associated with viral vector prime-boost systems.