Nilsson C, Mäkitalo B, Thorstensson R, Norley S, Binninger-Schinzel D, Cranage M, Rud E, Biberfeld G, Putkonen P
Swedish Institute for Infectious Disease Control and Microbiology and Tumourbiology Centre, Karolinska Institute, Stockholm.
AIDS. 1998 Dec 3;12(17):2261-70. doi: 10.1097/00002030-199817000-00006.
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.
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.
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.
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.
研究用减毒的猿猴免疫缺陷病毒（SIV）macC8 疫苗接种猕猴是否能诱导针对经直肠暴露于 SIVsm 以及经静脉暴露于差异更大的 HIV-2 的长期保护性免疫。
用减毒活 SIVmacC8 疫苗接种 8 个月后，4 只食蟹猴经直肠感染 SIVsm，另外 4 只接种疫苗的猴子经静脉感染 HIV-2。SIVmacC8 疫苗接种 16 个月后，另外 2 只猴子经直肠黏膜感染 SIVsm。首次感染后 8 个月，对 2 只显示对 SIVsm 有保护作用的接种疫苗动物再次进行攻击感染。10 只未接种疫苗的动物作为对照。监测血清抗原血症、病毒分离、抗体反应、细胞介导免疫以及 CD4+和 CD8+T 细胞亚群。采用基于聚合酶链反应（PCR）的检测方法区分病毒群体。
在攻击感染时，10 只接种疫苗动物中有 8 只 SIVmacC8 DNA 的 PCR 检测呈阳性，但外周血单个核细胞中未分离到病毒。SIVsm 攻击感染后，6 只接种疫苗动物中有 3 只 SIVsm PCR 检测反复呈阴性。在 3 只被感染的猴子中，有 1 只攻击感染病毒最初受到抑制，但该猴子在致病性病毒复制增加后最终发展为艾滋病。再次攻击感染的猴子仍受到保护。所有经 HIV-2 攻击感染的接种疫苗动物均发生双重感染。所有对照均感染了 SIVsm 或 HIV-2。在攻击感染时，接种疫苗动物有针对 SIVmac 的中和抗体，但未检测到针对 SIVsm 或 HIV-2 的明显交叉中和抗体。抗原结合抗体或中和抗体的滴度与保护作用无关。对 SIV Gag/Pol 的细胞毒性 T 细胞反应以及病毒特异性 T 细胞增殖反应较低。
减毒活 SIVmacC8 疫苗能够在一部分猕猴中诱导针对异源经直肠 SIVsm 攻击感染的长期保护作用，但不能保护经静脉感染的差异更大的 HIV-2。
