Highly Effective Control of an AIDS Virus Challenge in Macaques by Using Vesicular Stomatitis Virus and Modified Vaccinia Virus Ankara Vaccine Vectors in a Single-Boost Protocol
Highly Effective Control of an AIDS Virus Challenge in Macaques by Using Vesicular Stomatitis Virus and Modified Vaccinia Virus Ankara Vaccine Vectors in a Single-Boost Protocol
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通过在单次加强方案中使用水泡性口炎病毒和改良痘苗病毒安卡拉疫苗载体，高效控制猕猴中的艾滋病病毒挑战
作者：
E. Ramsburg;Nina F. Rose;P. Marx;Megan E. Mefford;D. Nixon;Walter J. Moretto;D. Montefiori;P. Earl;B. Moss;J. Rose
以前的研究已经表明，用编码猿猴免疫缺陷病毒-人免疫缺陷病毒（SHIV）杂交病毒的Env和Gag蛋白的减毒水泡性口炎病毒（VSV）载体对恒河猴进行疫苗接种和加强，在用高致病性SHIV 89.6P攻击后保护恒河猴免受AIDS（23）。在本研究中，我们比较了由表达SHIV Env、Gag和Pol蛋白的VSV载体组成的单次初免-加强方案与由VSV载体初免然后用表达相同SHIV蛋白的修饰的牛痘病毒安卡拉（MVA）单次加强组成的方案的有效性。用SHIV 89.6P攻毒后，MVA加强免疫的动物将攻毒病毒载量峰值控制在2 × 106拷贝/ml以下（该水平显著低于VSV加强免疫动物观察到的水平，也低于采用相同攻毒的其他疫苗研究报告的水平）。MVA加强的动物显示出极好的CD 4 + T细胞保存，而四只VSV加强的动物中有两只显示出CD 4 + T细胞的显著损失。MVA增强动物的保护作用增强与攻击前CD 8 + T细胞对SHIV抗原的反应增强和攻击后SHIV中和抗体产生增强的趋势相关。
ABSTRACT Previous studies have shown that vaccination and boosting of rhesus macaques with attenuated vesicular stomatitis virus (VSV) vectors encoding Env and Gag proteins of simian immunodeficiency virus-human immunodeficiency virus (SHIV) hybrid viruses protect rhesus macaques from AIDS after challenge with the highly pathogenic SHIV 89.6P (23). In the present study, we compared the effectiveness of a single prime-boost protocol consisting of VSV vectors expressing SHIV Env, Gag, and Pol proteins to that of a protocol consisting of a VSV vector prime followed with a single boost with modified vaccinia virus Ankara (MVA) expressing the same SHIV proteins. After challenge with SHIV 89.6P, MVA-boosted animals controlled peak challenge viral loads to less than 2 × 106 copies/ml (a level significantly lower than that seen with VSV-boosted animals and lower than those reported for other vaccine studies employing the same challenge). MVA-boosted animals have shown excellent preservation of CD4+ T cells, while two of four VSV-boosted animals have shown significant loss of CD4+ T cells. The improved protection in MVA-boosted animals correlates with trends toward stronger prechallenge CD8+-T-cell responses to SHIV antigens and stronger postchallenge SHIV-neutralizing antibody production.
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用两种不同的减毒疫苗对猕猴进行顺序免疫可诱导长期的病毒特异性免疫反应，并提供针对异源猿类人类免疫缺陷病毒（SHIV（89.6）P）引起的艾滋病的保护作用。
DOI：
10.1006/viro.2000.0695
发表时间：
2001
期刊：
Virology.
影响因子：
--
作者：
Kumar,A;Lifson,JD;Li,Z;Jia,F;Mukherjee,S;Adany,I;Liu,Z;Piatak,M;Sheffer,D;McClure,HM;Narayan,O
通讯作者：
Narayan,O
影响因子：
5.5
作者：
Amara, RR;Villinger, F;Robinson, HL
通讯作者：
Robinson, HL
影响因子：
56.9
作者：
Barouch, DH;Santra, S;Letvin, NL
通讯作者：
Letvin, NL
通过重组复制缺陷型牛痘病毒 MVA 启动和增强对呼吸道合胞病毒的免疫力。
影响因子：
5.5
作者：
Wyatt,LS;Whitehead,SS;Venanzi,KA;Murphy,BR;Moss,B
通讯作者：
Moss,B
影响因子：
3.7
作者：
Earl, PL;Wyatt, LS;Moss, B
通讯作者：
Moss, B