Simian-human immunodeficiency virus SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239 is independent of the route of immunization and is associated with a combination of cytotoxic T-lymphocyte and alpha interferon responses
Simian-human immunodeficiency virus SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239 is independent of the route of immunization and is associated with a combination of cytotoxic T-lymphocyte and alpha interferon responses
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DOI：
10.1128/jvi.77.5.3099-3118.2003
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发表时间：
2003-03-01
影响因子：
5.4
通讯作者：
Miller, CJ
中科院分区：
文献类型：
--
作者：
Abel, K;Compton, L;Miller, CJ
针对致病性猴免疫缺陷病毒(SIV)的攻击，灵长类减毒慢病毒疫苗提供了最一致的保护。因此，它们提供了一个很好的模型来检验免疫途径对攻击结果的影响，并研究疫苗诱导的保护性抗SIV免疫反应。在本研究中，用非致病性猴免疫缺陷病毒(SIV)89.6经静脉或粘膜(经鼻或经阴道)免疫恒河猴，然后在阴道内用致病性SIVmac239攻击。在长期全身感染非致病性疫苗病毒后，免疫途径不影响黏膜攻击结果。此外，对SIV挑战的保护与多种宿主免疫效应机制的诱导有关。对免疫保护动物和未接种保护动物的免疫反应的比较表明，在攻击后的急性期，接种保护动物的SIV Gag特异性细胞毒性T细胞和分泌干扰素的细胞频率较高。在攻击后的最初几周，接种了疫苗保护的动物的外周血单个核细胞干扰素-αmRNA水平也比接种非保护动物的增加得更明显。因此，先天和细胞的抗SIV免疫反应似乎有助于SHIV89.6诱导的对致病SIVmac239的阴道内攻击的保护。
Attenuated primate lentivirus vaccines provide the most consistent protection against challenge with pathogenic simian immunodeficiency virus (SIV). Thus, they provide an excellent model to examine the influence of the route of immunization on challenge outcome and to study vaccine-induced protective anti-SIV immune responses. In the present study, rhesus macaques were immunized with live nonpathogenic simian-human immunodeficiency virus (SHIV) 89.6 either intravenously or mucosally (intranasally or intravaginally) and then challenged intravaginally with pathogenic SIVmac239. The route of immunization did not affect mucosal challenge outcome after a prolonged period of systemic infection with the nonpathogenic vaccine virus. Further, protection from the SIV challenge was associated with the induction of multiple host immune effector mechanisms. A comparison of immune responses in vaccinated-protected and vaccinated-unprotected animals revealed that vaccinated-protected animals had higher frequencies of SIV Gag-specific cytotoxic T lymphocytes and gamma interferon (IFN-gamma)-secreting cells during the acute phase postchallenge. Vaccinated-protected animals also had a more pronounced increase in peripheral blood mononuclear cell IFN-alpha mRNA levels than did the vaccinated-unprotected animals in the first few weeks after challenge. Thus, innate as well as cellular anti-SIV immune responses appeared to contribute to the SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239.