病毒学
dna疫苗
生物
免疫原性
接种疫苗
猿猴免疫缺陷病毒
水泡性口炎病毒
改良安卡拉痘苗
埃利斯波特
免疫学
免疫系统
病毒
牛痘
重组DNA
T细胞
免疫
基因
生物化学
作者
Michael A. Egan,Siew Yen Chong,Shakuntala Megati,David C. Montefiori,Nina Rose,Jean Boyer,Maninder K. Sidhu,Jorge A. Quiróz,Margherita Rosati,Eva B. Schadeck,George N. Pavlakis,David B. Weiner,John K. Rose,Zimra R. Israel,Stephen A. Udem,John H. Eldridge
标识
DOI:10.1089/aid.2005.21.629
摘要
Of the various approaches being developed as prophylactic HIV vaccines, those based on a heterologous plasmid DNA prime, live vector boost vaccination regimen appear especially promising in the nonhuman primate/ simian–human immunodeficiency virus (SHIV) challenge model. In this study, we sought to determine whether a series of intramuscular priming immunizations with a plasmid DNA vaccine expressing SIVgag p39, in combination with plasmid expressed rhesus IL-12, could effectively enhance the immunogenicity and postchallenge efficacy of two intranasal doses of recombinant vesicular stomatitis virus (rVSV)-based vectors expressing HIV-1 env 89.6P gp160 and SIVmac239 gag p55 in rhesus macaques. In macaques receiving the combination plasmid DNA prime, rVSV boost vaccination regimen we observed significantly increased SIVgag- specific cell-mediated and humoral immune responses and significantly lower viral loads postintravenous SHIV89.6P challenge relative to macaques receiving only the rVSV vectored immunizations. In addition, the plasmid DNA prime, rVSV boost vaccination regimen also tended to increase the preservation of peripheral blood CD4+ cells and reduce the morbidity and mortality associated with SHIV89.6P infection. An analysis of immune correlates of protection after SHIV89.6P challenge revealed that the prechallenge SHIV-specific IFN-γ ELISpot response elicited by vaccination and the ability of the host to mount a virus-specific neutralizing antibody response postchallenge correlated with postchallenge clinical outcome. The correlation between vaccine-elicited cell-mediated immune responses and an improved clinical outcome after SHIV challenge provides strong justification for the continued development of a cytokine-enhanced plasmid DNA prime, rVSV vector boost immunization regimen for the prevention of HIV infection.
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