ALVAC-SIV-gag-pol-env-based vaccination and macaque major histocompatibility complex class I (A*01) delay simian immunodeficiency virus SIVmac-induced immunodeficiency
ALVAC-SIV-gag-pol-env-based vaccination and macaque major histocompatibility complex class I (A*01) delay simian immunodeficiency virus SIVmac-induced immunodeficiency
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DOI：
10.1128/jvi.76.1.292-302.2002
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发表时间：
2002-01-01
影响因子：
5.4
通讯作者：
Franchini, G
中科院分区：
文献类型：
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作者：
Pal, R;Venzon, D;Franchini, G
t细胞介导的免疫效应机制在抑制人类免疫缺陷病毒/猴免疫缺陷病毒（HIV/SIV）感染后的复制中起着重要作用。疫苗接种和感染诱导的t细胞反应都依赖于宿主主要组织相容性复合体I类和II类（MHC-I和MHC-II）抗原。在这里，我们报告了固有的，宿主依赖的免疫应答SIVmac251感染和疫苗诱导的免疫应答病毒抗原能够减少病毒复制和/或CD4(+) t细胞损失。MHC-I Mamu-A*01基因型的存在和alvac - siv -gag- polo -env （ALVAC-SIV-gpe）疫苗的接种都有助于在初次感染期间限制SIVmac251的复制，保存CD4(+) T细胞，并延迟疾病进展；动物对SIVmac251的直肠内攻击暴露（(561)）。alvac - siv - gv免疫在67%的免疫动物中累积诱导细胞毒性t淋巴细胞（CTL）反应。在病毒攻击后，在接种疫苗的猕猴中观察到显著的继发性病毒特异性CD8(+) t细胞应答。在相同的免疫猕猴中，观察到在初次感染期间病毒载量下降（P = 0.0078），在急性和慢性感染期间对CD4细胞损失的保护（P = 0.0099和P = 0.03）。还观察到接种疫苗的猕猴存活率提高的趋势。无论是通过gp120免疫增强ALVAC-SIV-gpe，还是通过粘膜和全身免疫途径联合接种疫苗，都不能显著提高ALVAC-SIV-gpe疫苗的保护作用。在评估MHC-I Mamu-A*01单独在限制未接种SIV分离物攻击后的病毒血症中的作用时，我们观察到，静脉注射SIVmac251（561）或SIVSME660攻击后，MamuA*01阳性猕猴的病毒载量并没有显著降低。然而，在每组Mamu-A*01阳性的猕猴中，CD4(+) t细胞损失均有显著延迟。有趣的是，分别用SIV/HIV嵌合毒株SHIV89.6P或SHIVKU2进行静脉或直肠内攻击的情况下，MHC-I Mamu-A*01阳性的猕猴并没有显著限制原发性病毒血症。Mamu-A*01分子的保护作用与B*5701 HLA等位基因对hiv -1感染者的保护作用相似，需要在评估疫苗对SIV攻击模型的有效性时加以考虑。
T-cell-mediated immune effector mechanisms play an important role in the containment of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) replication after infection. Both vaccination- and infection-induced T-cell responses are dependent on the host major histocompatibility complex classes I and II (MHC-I and MHC-II) antigens. Here we report that both inherent, host-dependent immune responses to SIVmac251 infection and vaccination-induced immune responses to viral antigens were able to reduce virus replication and/or CD4(+) T-cell loss. Both the presence of the MHC-I Mamu-A*01 genotype and vaccination of rhesus macaques with ALVAC-SIV-gag-pol-env (ALVAC-SIV-gpe) contributed to the restriction of SIVmac251 replication during primary infection, preservation of CD4(+) T cells, and delayed disease progression following ;intrarectal challenge exposure of the animals to SIVmac251 ((561)). ALVAC-SIV-gpe immunization induced cytotoxic T-lymphocyte (CTL) responses cumulatively in 67% of the immunized animals. Following viral challenge, a significant secondary virus-specific CD8(+) T-cell response was observed in the vaccinated macaques. In the same immunized macaques, a decrease in virus load during primary infection (P = 0.0078) and protection from CD4 loss during both acute and chronic phases of infection (P = 0.0099 and P = 0.03, respectively) were observed. A trend for enhanced survival of the vaccinated macaques was also observed. Neither boosting the ALVAC-SIV-gpe with gp120 immunizations nor administering the vaccine by the combination of mucosal and systemic immunization routes increased significantly the protective effect of the ALVAC-SIV-gpe vaccine. While assessing the role of MHC-I Mamu-A*01 alone in the restriction of viremia following challenge of nonvaccinated animals with other SIV isolates, we observed that the virus load was not significantly lower in MamuA*01-positive macaques following intravenous challenge with either SIVmac251 (561) or SIVSME660. However, a significant delay in CD4(+) T-cell loss was observed in Mamu-A*01-positive macaques in each group. Of interest, in the case of intravenous or intrarectal challenge with the chimeric SIV/HIV strains SHIV89.6P or SHIVKU2, respectively, MHC-I Mamu-A*01-positive macaques did not significantly restrict primary viremia. The finding of the protective effect of the Mamu-A*01 molecule parallels the protective effect of the B*5701 HLA allele in HIV-1-infected humans and needs to be accounted for in the evaluation of vaccine efficacy against SIV challenge models.