Priming-boosting vaccination with recombinant Mycobacterium bovis bacillus Calmette-Guerin and a nonreplicating vaccinia virus recombinant leads to long-lasting and effective immunity
Priming-boosting vaccination with recombinant Mycobacterium bovis bacillus Calmette-Guerin and a nonreplicating vaccinia virus recombinant leads to long-lasting and effective immunity
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DOI：
10.1128/jvi.79.20.12871-12879.2005
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发表时间：
2005-10-01
影响因子：
5.4
通讯作者：
Honda, M
中科院分区：
文献类型：
--
作者：
Ami, Y;Izumi, Y;Honda, M
病毒特异性t细胞反应可以限制1型免疫缺陷病毒（HIV-1）的传播并预防疾病进展，因此可以作为人类负担得起、安全有效的疫苗的基础。为了评估它们作为疫苗的潜力，我们使用牛分枝杆菌卡介苗(BCG)-Tokyo和复制缺陷牛痘病毒株（DIs）作为载体，表达猴免疫缺陷病毒（siv） （rBCG-SIVgag和rDIsSIVgag）的全长gag。在食蟹猕猴身上接种rBCG-SIVgag作为单一方式或与rDIsSIVgag联合静脉注射。将rBCG-SIVgag注入猕猴，然后用rDIsSIVgag增强猕猴，可诱导高水平的特异性SIV Gag γ干扰素（ifn - γ）斑点形成细胞。在对猕猴进行为期1年的观察中，这种联合治疗方案对致病性猿人免疫缺陷病毒的粘膜攻击产生了有效的保护性免疫。抗原特异性细胞内ifn - γ活性在每只猕猴中都有相似的诱导。其他接受相反组合或单模态疫苗的人群没有得到有效保护。这些结果表明，重组牛分枝杆菌bcg载体与复制缺陷痘苗病毒DIs载体在启动增强策略中联合施用时，可能具有作为HIV/AIDS疫苗的潜力。
Virus-specific T-cell responses can limit immunodeficiency virus type 1 (HIV-1) transmission and prevent disease progression and so could serve as the basis for an affordable, safe, and effective vaccine in humans. To assess their potential for a vaccine, we used Mycobacterium bovis bacillus Calmette-Guerin (BCG)-Tokyo and a replication-deficient vaccinia virus strain (DIs) as vectors to express full-length gag from simian immunodeficiency viruses (SIVs) (rBCG-SIVgag and rDIsSIVgag). Cynomolgus macaques were vaccinated with either rBCG-SIVgag dermally as a single modality or in combination with rDIsSIVgag intravenously. When cynomologus macaques were primed with rBCG-SIVgag and then boosted with rDIsSIVgag, high levels of gamma interferon (IFN-gamma) spot-forming cells specific for SIV Gag were induced. This combination regimen elicited effective protective immunity against mucosal challenge with pathogenic simian-human immunodeficiency virus for the 1 year the macaques were under observation. Antigen-specific intracellular IFN-gamma activity was similarly induced in each of the macaques with the priming-boosting regimen. Other groups receiving the opposite combination or the single-modality vaccines were not effectively protected. These results suggest that a recombinant M. bovis BCG-based vector may have potential as an HIV/AIDS vaccine when administered in combination with a replication-deficient vaccinia virus DIs vector in a priming-boosting strategy.