Improved protection against simian immunodeficiency virus mucosal challenge in macaques primed with a DNA vaccine and boosted with the recombinant modified vaccinia virus Ankara and recombinant Semliki Forest virus

Improved protection against simian immunodeficiency virus mucosal challenge in macaques primed with a DNA vaccine and boosted with the recombinant modified vaccinia virus Ankara and recombinant Semliki Forest virus
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DOI:
10.1016/j.vaccine.2007.11.025
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发表时间:
2008-01-24
期刊:
影响因子:
5.5
通讯作者:
Le Grand, Roger
Le Grand, Roger
中科院分区:
医学3区
文献类型:
--
作者:
Martinon, Frederic;Brochard, Patricia;Le Grand, Roger

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以猴免疫缺陷病毒(SIV)实验感染食食猴作为人免疫缺陷病毒感染的模型,研究了DNA与表达SIV gag、pol、env、tat、rev和nef的修饰重组痘苗病毒(MVA)和Semliki Forest病毒(SFV)结合的疫苗策略的免疫原性和保护效果。虽然这种免疫策略诱导了中等程度的免疫应答,但接种疫苗明显改善了粘膜攻击后致病性SIVmac251感染的控制。在感染的急性阶段,接种疫苗的动物的病毒蟾蜍减少了2个百分点,在6只猕猴中,有5只猕猴的病毒载量低于设定值的检测极限。没有发现与免疫保护相关的因素,但在接种疫苗的动物中检测到siv特异性t细胞反应比对照组更早。这些结果突出了减毒活病毒载体在疫苗接种策略中的作用。(C) 2007 Elsevier Ltd.版权所有。
Using the experimental infection of cynomolgus macaques with simian immunodeficiency virus (SIV) as a model of human immunodeficiency virus infection in humans, we studied the immunogenicity and protective efficacy of a vaccine strategy combining DNA, the modified recombinant vaccinia virus strain Ankara (MVA) and Semliki Forest virus (SFV) expressing gag, pol, env, tat, rev and nef from SIV. Although this immunization strategy induced moderate immune responses, the control of pathogenic SIVmac251 infection following mucosal challenge was clearly improved by vaccination. The viral toad in vaccinated animals was reduced by 2 togs during the acute phase of infection and, in five of the six macaques, viral load felt below the detection limit at set point. No correlates of immune protection were identified, but SIV-specific T-cell responses were detected earlier in vaccinated animals than in controls. These results highlight the power of live attenuated virus vectors for vaccination strategies. (C) 2007 Elsevier Ltd. All rights reserved.