Live attenuated simian immunodeficiency virus (SIV)mac in macaques can induce protection against mucosal infection with SIVsm
Live attenuated simian immunodeficiency virus (SIV)mac in macaques can induce protection against mucosal infection with SIVsm
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DOI：
10.1097/00002030-199817000-00006
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发表时间：
1998-12-03
期刊：
影响因子：
3.8
通讯作者：
Putkonen, P
中科院分区：
文献类型：
--
作者：
Nilsson, C;Mäkitalo, B;Putkonen, P
目的：研究猴免疫缺陷病毒（simian immunodeficiency virus，SIVmacC 8）减毒疫苗能否诱导猴产生长期保护性免疫，以对抗SIVsm直肠感染和HIV-2静脉感染。设计和方法：SIVmacC 8减毒活疫苗接种8个月后，分别用SIVsm直肠感染和HIV-2静脉感染4只猕猴。在SIVmacC 8疫苗接种后16个月，另外两只猴子用SIVsm穿过直肠粘膜进行攻击。两名被证明对SIVsm有保护作用的疫苗接种者在第一次攻击后8个月再次攻击。10只未处理动物用作对照。监测血清抗原血症、病毒分离、抗体应答、细胞介导的免疫以及CD 4+和CD 8 + T细胞亚群。PCR为基础的测定被用来区分病毒population.Results：在挑战的时候，10个疫苗接种者中有8个是PCR阳性的SIVmacC 8 DNA，但没有病毒可以从外周血单个核细胞中分离出来。在SIVsm攻击后，6名疫苗接种者中有3名反复为SIVsm PCR阴性。在三只受感染的猴子中，其中一只猴子的攻击病毒最初受到抑制，但在致病病毒复制增加后，猴子最终发展为艾滋病。重新激发的猴子仍然受到保护。所有HIV-2挑战的接种者都成为双重感染者。所有对照组感染SIVsm或HIV-2。在攻毒时，疫苗接种者具有SIVmac中和抗体，但没有可证实的SIVsm或HIV-2交叉中和抗体。抗原结合或中和抗体的滴度与保护无关。SIV Gag/Pol和病毒特异性T细胞增殖反应的细胞毒性T细胞反应是low.Conclusion：减毒SIVmacC 8活疫苗能够诱导长期保护对异源直肠内SIVsm的挑战在一定比例的猕猴，但不是对更分散的HIV-2，这是静脉注射。(C)1998年利平科特·威廉姆斯和威尔金斯。
Objective: To investigate whether vaccination of macaques with attenuated simian immunodeficiency virus (SIV)macC8 could induce long-term protective immunity against rectal exposure to SIVsm and intravenous exposure to the more divergent HIV-2.Design and methods: Eight months after vaccination with live attenuated SIVmacC8, four cynomolgus monkeys were challenged with SIVsm intrarectally and another four vaccinated monkeys were challenged with HIV-2 intravenously. Sixteen months after SIVmacC8 vaccination, another two monkeys were challenged with SIVsm across the rectal mucosa. Two vaccinees shown to be protected against SIVsm were rechallenged 8 months after the first challenge. Ten naive animals were used as controls. Serum antigenaemia, virus isolation, antibody responses, cell-mediated immunity and CD4+ and CD8+ T-cell subpopulations were monitored. PCR-based assays were used to distinguish between virus populations.Results: At the time of challenge, eight out of 10 vaccinees were PCR-positive for SIVmacC8 DNA but no virus could be isolated from peripheral blood mononuclear cells. After SIVsm challenge, three out of six vaccinees were repeatedly SIVsm PCR-negative. In one of the three infected monkeys, the challenge virus was initially suppressed but the monkey ultimately developed AIDS after increased replication of the pathogenic virus. Rechallenged monkeys remained protected. All HIV-2-challenged vaccinees became superinfected. All controls became infected with either SIVsm or HIV-2. At the time of challenge the vaccinees had neutralizing antibodies to SIVmac but no demonstrable cross-neutralizing antibodies to SIVsm or HIV-2. Titres of antigen-binding or neutralizing antibodies did not correlate with protection. Cytotoxic T-cell responses to SIV Gag/Pol and virus-specific T-cell proliferative responses were low.Conclusion: The live attenuated SIVmacC8 vaccine was able to induce long-term protection against heterologous intrarectal SIVsm challenge in a proportion of macaques but not against the more divergent HIV-2, which was given intravenously. (C) 1998 Lippincott Williams & Wilkins.