Sequential immunization of macaques with two differentially attenuated vaccines induced long-term virus-specific immune responses and conferred protection against AIDS caused by heterologous simian human immunodeficiency Virus (SHIV(89.6)P).
Sequential immunization of macaques with two differentially attenuated vaccines induced long-term virus-specific immune responses and conferred protection against AIDS caused by heterologous simian human immunodeficiency Virus (SHIV(89.6)P).
复制标题
用两种不同的减毒疫苗对猕猴进行顺序免疫可诱导长期的病毒特异性免疫反应，并提供针对异源猿类人类免疫缺陷病毒（SHIV（89.6）P）引起的艾滋病的保护作用。
DOI：
10.1006/viro.2000.0695
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
Narayan,O
中科院分区：
文献类型：
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作者：
Kumar,A;Lifson,JD;Li,Z;Jia,F;Mukherjee,S;Adany,I;Liu,Z;Piatak,M;Sheffer,D;McClure,HM;Narayan,O
用活疫苗ΔvpuΔnefSHIV-4（疫苗-I）和Δvpu SHIVPPC（疫苗-II）顺序免疫4只恒河猴。疫苗病毒在接种疫苗动物的外周血单核细胞（PBMCs）中没有有效复制。所有4只动物均产生了针对疫苗-I和-II包膜糖蛋白的结合抗体，但仅产生了针对疫苗-I的中和抗体。他们开发了疫苗病毒特异性CTL，也可以识别同源和异源致病性SHIV。最后一次免疫后30周，用高毒力异源SHIV 89.6P对接种疫苗的动物和3只未接种疫苗的对照动物进行iv攻击。与预期一致，3只未接种疫苗的对照动物出现大量感染性PBMC、高血浆病毒血症和CD 4 +T细胞急剧丢失。两个对照组没有产生任何免疫反应，并在大约6个月内死于艾滋病。第三只对照动物产生了中和抗体，病程更慢性，但最终在接种后81周死于艾滋病相关并发症。如PBMC中存在攻毒病毒特异性DNA和血浆中存在RNA所示，4只接种动物感染攻毒病毒。然而，这些动物中的病毒复制效率比对照动物低约200- 60，000倍，最终，在4只接种组中的3只中，血浆病毒RNA变得不可检测。在攻毒后第3周出现一过性下降后，动物在整个85周的观察期内维持正常的CD 4 + T细胞水平。在整个观察期间，它们也保持CTL应答。因此，这些研究表明，分级免疫方案导致安全和高效的持久免疫应答，这与高致病性异源SHIV89.6P对AIDS的保护有关。
Four rhesus macaques were sequentially immunized with live vaccines ΔvpuΔnefSHIV-4 (vaccine-I) and Δvpu SHIVPPC(vaccine-II). The vaccine viruses did not replicate productively in the peripheral blood mononuclear cells (PBMCs) of the vaccinated animals. All four animals developed binding antibodies against both the vaccine-I and -II envelope glycoproteins but neutralizing antibodies only against vaccine-I. They developed vaccine virus-specific CTLs that also recognized homologous as well as heterologous pathogenic SHIVs. Thirty weeks after the last immunization, the vaccinated animals and three unvaccinated control animals were challenged iv with a highly virulent heterologous SHIV89.6P. As expected, the three unvaccinated control animals developed large numbers of infectious PBMCs, high plasma viremia, and precipitous loss of CD4+T cells. Two controls did not develop any immune response and succumbed to AIDS in about 6 months. The third control animal developed neutralizing antibodies and had a more chronic disease course, but eventually succumbed to AIDS-related complications 81 weeks after inoculation. The four vaccinated animals became infected with challenge virus as indicated by the presence of challenge virus-specific DNA in the PBMCs and RNA in plasma. However, virus in these animals replicated approximately 200- to 60,000-fold less efficiently than in control animals and eventually, plasma viral RNA became undetectable in three of the four vaccinates. The animals maintained normal CD4+T-cell levels throughout the observation period of 85 weeks after a transient drop at Week 3 postchallenge. They also maintained CTL responses throughout the observation period. These studies thus showed that the graded immunization schedule resulted in a safe and highly effective long-lasting immune response that was associated with protection against AIDS by highly pathogenic heterologous SHIV89.6P.