Uberla Klaus, Rosenwirth Brigitte, Ten Haaft Peter, Heeney Jonathan, Sutter Gerd, Erfle Volker
Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany.
J Med Primatol. 2007 Feb;36(1):2-9. doi: 10.1111/j.1600-0684.2006.00190.x.
The long-term benefits of highly active antiretroviral therapy in HIV-infected patients are limited by emergence of drug-resistant variants and side effects. Therefore, we studied the concept of therapeutic immunization in 18 rhesus monkeys infected with a highly pathogenic simian immunodeficiency virus (SIV) swarm.
Monkeys were treated with the reverse transcriptase inhibitor (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) for 19 weeks starting 10 days after infection. After suppression of viremia, one group of monkeys was immunized with recombinant modified vaccinia virus Ankara (MVA) vectors expressing gag-pol and env. A second group received MVA vectors expressing the regulatory genes tat, rev and nef, while a third group was not immunized.
Immunization with gag-pol and env expressing MVA enhanced SIV antibody titers. Following discontinuation of PMPA treatment, a rebound in viral load was observed. However, in three of six monkeys immunized with MVA gag-pol and MVA env, and two of six monkeys immunized MVA expressing regulatory genes set point RNA levels were below or close to a threshold level of 10(4) RNA copies/ml, while only one of six unvaccinated monkeys maintained such low RNA levels.
Although a subset of animals seem to benefit from therapeutic immunization with MVA vectors, the difference in set point RNA levels between the groups did not reach statistical significance.
高效抗逆转录病毒疗法对HIV感染患者的长期益处受到耐药变异体出现和副作用的限制。因此，我们在18只感染高致病性猿猴免疫缺陷病毒（SIV）群体的恒河猴中研究了治疗性免疫的概念。
猴子在感染后10天开始用逆转录酶抑制剂（R）-9-（2-膦酰甲氧基丙基）腺嘌呤（PMPA）治疗19周。在病毒血症得到抑制后，一组猴子用表达gag-pol和env的重组改良安卡拉痘苗病毒（MVA）载体进行免疫。第二组接受表达调节基因tat、rev和nef的MVA载体，而第三组未进行免疫。
用表达gag-pol和env的MVA免疫可提高SIV抗体滴度。在停止PMPA治疗后，观察到病毒载量反弹。然而，在接受MVA gag-pol和MVA env免疫的6只猴子中的3只，以及接受表达调节基因的MVA免疫的6只猴子中的2只，设定点RNA水平低于或接近10⁴RNA拷贝/毫升的阈值水平，而在6只未接种疫苗的猴子中只有1只维持如此低的RNA水平。
尽管一部分动物似乎从用MVA载体进行的治疗性免疫中受益，但各组之间设定点RNA水平的差异未达到统计学意义。
