Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine.
Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine.
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DOI：
10.1093/ofid/ofw034
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发表时间：
2016-01
影响因子：
4.2
通讯作者：
Amara RR
中科院分区：
文献类型：
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作者：
Chamcha V;Kannanganat S;Gangadhara S;Nabi R;Kozlowski PA;Montefiori DC;LaBranche CC;Wrammert J;Keele BF;Balachandran H;Sahu S;Lifton M;Santra S;Basu R;Moss B;Robinson HL;Amara RR
背景：在这项研究中，我们分析了猴免疫缺陷病毒（SIV）猕猴239（SIVmac 239）类似物的临床试验GOVX-B11脱氧核糖核酸（DNA）/改良安卡拉牛痘（MVA）人类免疫缺陷病毒疫苗的保护效果。 方法：试验疫苗使用了一种突变的DNA免疫原来模拟人类疫苗，并在第0周和第8周给予DNA，在第16周和第32周给予MVA。 在最后一次免疫后6个月开始，用0.3动物感染剂量的SIV mangabey E660（SIVsmE 660）进行12次每周直肠攻击。结果：在前6次直肠暴露于SIVsmE 660后，<10岁的TRIM 5 α-容许恒河猴的每次暴露感染风险降低了80%，而10岁以上的动物降低了46%;在12次攻击后，它们显示了72%，而不是10%的降低。 对引发的免疫反应的分析表明，年轻动物中较高的抗体反应在保护中发挥了作用。结论：GOVX-B11 HIV的猿猴类似物对年轻成年猕猴的重复直肠攻击提供了强有力的保护。
Background. In this study, we analyzed the protective efficacy of a simian immunodeficiency virus (SIV) macaque 239 (SIVmac239) analogue of the clinically tested GOVX-B11 deoxyribonucleic acid (DNA)/modified vaccinia Ankara (MVA) human immunodeficiency virus vaccine. Methods. The tested vaccine used a DNA immunogen mutated to mimic the human vaccine and a regimen with DNA deliveries at weeks 0 and 8 and MVA deliveries at weeks 16 and 32. Twelve weekly rectal challenges with 0.3 animal infectious doses of SIV sootey mangabey E660 (SIVsmE660) were administered starting at 6 months after the last immunization. Results. Over the first 6 rectal exposures to SIVsmE660, <10-year-old tripartite motif-containing protein 5 (TRIM5)α-permissive rhesus macaques showed an 80% reduction in per-exposure risk of infection as opposed to a 46% reduction in animals over 10 years old; and, over the 12 challenges, they showed a 72% as opposed to a 10% reduction. Analyses of elicited immune responses suggested that higher antibody responses in the younger animals had played a role in protection. Conclusions. The simian analogue of the GOVX-B11 HIV provided strong protection against repeated rectal challenges in young adult macaques.