SIVmac239 MVA vaccine with and without a DNA prime, similar prevention of infection by a repeated dose SIVsmE660 challenge despite different immune responses.
SIVmac239 MVA vaccine with and without a DNA prime, similar prevention of infection by a repeated dose SIVsmE660 challenge despite different immune responses.
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DOI：
10.1016/j.vaccine.2011.12.026
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发表时间：
2012-02-21
期刊：
影响因子：
5.5
通讯作者：
Robinson, Harriet L.
中科院分区：
文献类型：
--
作者：
Lai, Lilin;Kwa, Sue-Fen;Kozlowski, Pamela A.;Montefiori, David C.;Nolen, Tracy L.;Hudgens, Michael G.;Johnson, Welkin E.;Ferrari, Guido;Hirsch, Vanessa M.;Felber, Barbara K.;Pavlakis, George N.;Earl, Patricia L.;Moss, Bernard;Amara, Rama Rao;Robinson, Harriet L.
关键词：
使用不同试剂进行初免和加强的疫苗方案已经变得流行，以增强候选HIV/AIDS疫苗引起的T细胞和Ab应答。在这里，我们使用猿猴模型，以评估免疫原性和保护效力的重组修饰的牛痘安卡拉（MVA）疫苗的存在和不存在的重组DNA引物。猴疫苗和治疗方案代表了目前正在进行临床试验的候选HIV疫苗的原型。重组DNA和MVA免疫原表达猴免疫缺陷病毒（SIV）mac 239 Gag、PR、RT和Env序列。疫苗时间表测试了在第0、2和6个月接种MVA（MMM方案）或在第0和2个月用DNA初免并在第4和6个月用MVA加强（DDMM方案）。在最后一次免疫后6个月开始用异源SIV smE 660进行12次每周直肠攻击。两种方案引起相似的SIVsmE 660传播的每次挑战风险降低61-64%，尽管提高了不同的免疫应答模式。DDMM方案引起更高量级的CD 4 T细胞，而MMM方案在直肠分泌物中引起更高滴度和更大亲合力Env特异性IgG以及更频繁和更高滴度的SIV特异性伊加。两种方案均引起类似程度的CD 8 T细胞。T细胞反应的强度、直肠伊加Ab的特异性活性以及中和和抗体依赖性细胞毒性的检测特异性与感染风险无关。然而，Env特异性IgG的亲合力与每次攻击的获得风险具有强相关性，但仅针对DDMM组。我们的结论是，对于恒河猴中测试的免疫原，更简单的MMM方案是更复杂的DDMM方案的保护。
Vaccine regimens using different agents for priming and boosting have become popular for enhancing T cell and Ab responses elicited by candidate HIV/AIDS vaccines. Here we use a simian model to evaluate immunogenicity and protective efficacy of a recombinant modified vaccinia Ankara (MVA) vaccine in the presence and absence of a recombinant DNA prime. The simian vaccines and regimens represent prototypes for candidate HIV vaccines currently undergoing clinical testing. Recombinant DNA and MVA immunogens expressed simian immunodeficiency virus (SIV)mac239 Gag, PR, RT, and Env sequences. Vaccine schedules tested inoculations of MVA at months 0, 2, and 6 (MMM regimen) or priming with DNA at months 0 and 2 and boosting with MVA at months 4 and 6 (DDMM regimen). Twelve weekly rectal challenges with the heterologous SIV smE660 were initiated at 6 months following the last immunization. Both regimens elicited similar 61–64% reductions in the per challenge risk of SIVsmE660 transmission despite raising different patterns of immune responses. The DDMM regimen elicited higher magnitudes of CD4 T cells whereas the MMM regimen elicited higher titers and greater avidity Env-specific IgG and more frequent and higher titer SIV-specific IgA in rectal secretions. Both regimens elicited similar magnitudes of CD8 T cells. Magnitudes of T cell responses, specific activities of rectal IgA Ab, and the tested specificities for neutralization and antibody-dependent cellular cytotoxicity did not correlate with risk of infection. However, the avidity of Env-specific IgG had a strong correlation with the per challenge risk of acquisition, but only for the DDMM group. We conclude that for the tested immunogens in rhesus macaques, the simpler MMM regimen is as protective as the more complex DDMM regimen.
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影响因子：
5.4
作者：
Pancera, Marie;McLellan, Jason S.;Kwong, Peter D.
通讯作者：
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影响因子：
3.7
作者：
Pollara, Justin;Hart, Lydia;Brewer, Faraha;Pickeral, Joy;Packard, Beverly Z.;Hoxie, James A.;Komoriya, Akira;Ochsenbauer, Christina;Kappes, John C.;Roederer, Mario;Huang, Ying;Weinhold, Kent J.;Tomaras, Georgia D.;Haynes, Barton F.;Montefiori, David C.;Ferrari, Guido
通讯作者：
Ferrari, Guido
DOI：
10.1084/jem.20082831
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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2.2
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影响因子：
5.4
作者：
Holl, Vincent;Peressin, Maryse;Moog, Christiane
通讯作者：
Moog, Christiane