Risk of Immunodeficiency Virus Infection May Increase with Vaccine-Induced Immune Response
Risk of Immunodeficiency Virus Infection May Increase with Vaccine-Induced Immune Response
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DOI：
10.1128/jvi.00796-12
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发表时间：
2012-10-01
影响因子：
5.4
通讯作者：
Uberla, Klaus
中科院分区：
文献类型：
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作者：
Tenbusch, Matthias;Ignatius, Ralf;Uberla, Klaus
为了探讨新型补充素-增强免疫方案在非人类灵长类动物HIV感染模型中的有效性，用不同的DNA疫苗免疫恒河猴，用病毒样颗粒(VLP)加强免疫，然后用反复低剂量直肠暴露于猴免疫缺陷病毒(SIV)进行攻击。VLP加强免疫后细胞免疫反应的特征是在灭活的SIV颗粒刺激后产生大量SIV特异性的干扰素分泌细胞，而不是SIV多肽，并且缺乏可检测到的CD8(+)T细胞反应。在所有动物中都能诱导出针对SIV Gag和SIV Env的抗体，但与攻击时较差的中和活性一致，接种疫苗的猴子没有受到感染的保护，也没有控制病毒血症。令人惊讶的是，在重复的低剂量暴露中，具有大量SIV特异性伽马干扰素分泌细胞的接种者感染最快，而接种疫苗的猕猴中这些免疫细胞的数量与感染的易感性有关。因此，在缺乏保护性抗体或细胞毒性T细胞反应的情况下，疫苗诱导的免疫反应可能会增加获得免疫缺陷病毒感染的易感性。这一结果与病毒特异性T辅助细胞介导这种有害效应并导致过去HIV疫苗接种无效的假设是一致的(例如，STEP研究)。
To explore the efficacy of novel complementary prime-boost immunization regimens in a nonhuman primate model for HIV infection, rhesus monkeys primed by different DNA vaccines were boosted with virus-like particles (VLP) and then challenged by repeated low-dose rectal exposure to simian immunodeficiency virus (SIV). Characteristic of the cellular immune response after the VLP booster immunization were high numbers of SIV-specific, gamma interferon-secreting cells after stimulation with inactivated SIV particles, but not SIV peptides, and the absence of detectable levels of CD8(+) T cell responses. Antibodies specific to SIV Gag and SIV Env could be induced in all animals, but, consistent with a poor neutralizing activity at the time of challenge, vaccinated monkeys were not protected from acquisition of infection and did not control viremia. Surprisingly, vaccinees with high numbers of SIV-specific, gamma interferon-secreting cells were infected fastest during the repeated low-dose exposures and the numbers of these immune cells in vaccinated macaques correlated with susceptibility to infection. Thus, in the absence of protective antibodies or cytotoxic T cell responses, vaccine-induced immune responses may increase the susceptibility to acquisition of immunodeficiency virus infection. The results are consistent with the hypothesis that virus-specific T helper cells mediate this detrimental effect and contribute to the inefficacy of past HIV vaccination attempts (e. g., STEP study).