Arthur L O, Bess J W, Urban R G, Strominger J L, Morton W R, Mann D L, Henderson L E, Benveniste R E
AIDS Vaccine Program, PRI/DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
J Virol. 1995 May;69(5):3117-24. doi: 10.1128/JVI.69.5.3117-3124.1995.
Macaques immunized with uninfected human cells have been shown to be protected from challenge with simian immunodeficiency virus (SIV) propagated in human cells. To identify the potential antigens involved in this protection, macaques were immunized with uninfected human cells, sucrose density gradient-purified culture fluid from uninfected human cells (mock virus), beta-2 microglobulin (beta 2M), immunoaffinity-purified HLA class I and class II proteins from these human cells, and adjuvant. Although all macaques immunized with beta 2M and HLA class I developed high antibody titers to beta 2M, these animals were not protected from a subsequent challenge with infectious SIV grown in human cells. In contrast, the macaques immunized with class II protein (HLA-DR) and mock virus developed antibodies to class II protein and were protected from the intravenous infectious virus challenge. The class II protein- and mock virus-immunized animals which were protected from challenge were given boosters of the appropriate antigen and challenged with the same SIV propagated in macaque cells. All animals became infected, indicating that the protection seen with human class II protein did not extend to protection from infection with SIV containing macaque class II proteins. Since the virus released from SIV-infected macaque cells would contain macaque class II proteins, our results suggest that the initial SIV infected was completely prevented. In addition, the lack of protection from challenge with SIV propagated in macaque cells provided strong evidence that the protection was due to an immune response to the cellular proteins and not to epitopes cross-reactive between class II proteins and the viral proteins, since the identical virus proteins were present in both challenge stocks. These results are the first demonstration that immunization with a purified cellular protein can protect from virus infection.
已证明，用未感染的人类细胞免疫的猕猴可免受在人类细胞中繁殖的猿猴免疫缺陷病毒（SIV）的攻击。为了确定参与这种保护作用的潜在抗原，用未感染的人类细胞、未感染的人类细胞经蔗糖密度梯度纯化的培养液（模拟病毒）、β2微球蛋白（β2M）、从这些人类细胞中免疫亲和纯化的HLA I类和II类蛋白以及佐剂对猕猴进行免疫。尽管所有用β2M和HLA I类免疫的猕猴都产生了针对β2M的高抗体滴度，但这些动物并未免受随后用人细胞中生长的传染性SIV攻击。相比之下，用II类蛋白（HLA-DR）和模拟病毒免疫的猕猴产生了针对II类蛋白的抗体，并免受静脉内感染性病毒攻击。对免受攻击的用II类蛋白和模拟病毒免疫的动物给予适当抗原加强免疫，并用人细胞中繁殖的相同SIV进行攻击。所有动物均被感染，这表明人类II类蛋白所提供的保护作用并不延伸至免受含猕猴II类蛋白的SIV感染。由于从感染SIV的猕猴细胞中释放的病毒将含有猕猴II类蛋白，我们的结果表明最初的SIV感染被完全预防。此外，对猕猴细胞中繁殖的SIV攻击缺乏保护作用，这有力地证明了这种保护作用是由于对细胞蛋白的免疫反应，而不是由于II类蛋白与病毒蛋白之间的交叉反应表位，因为两种攻击毒株中都存在相同的病毒蛋白。这些结果首次证明用纯化的细胞蛋白免疫可预防病毒感染。
