Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 422 Curie Blvd., Philadelphia, PA 19104, United States.
Vaccine. 2010 Feb 23;28(8):1924-31. doi: 10.1016/j.vaccine.2009.10.100.
It has long been postulated that while CD8 lymphocytes are capable of suppressing human immunodeficiency virus (HIV)-1 replication it is unlikely that the viral reservoirs once formed can be cleared. Our previous studies demonstrate that co-immunizing cynomologous macaques with a simian/human immunodeficiency virus (SHIV) DNA-based vaccines induces a strong cellular immune response that is able to suppress viral replication. We further demonstrated that interleukin (IL)-12 could significantly enhance the vaccine specific CD8 lymphocyte response. In this manuscript cynomologous macaques were vaccinated with a SHIV DNA-based vaccine co-delivered with IL-12. The macaques were then challenged with SHIV89.6p. Two years post-immunization and viral challenge we transiently depleted CD8(+) T cells. Plasma viral load increased, demonstrating the central role of CD8(+) T cells in viral suppression yet an inability to clear the viral reservoirs. Furthermore, in the data presented here, we found a higher number of IFN-gamma producing vaccine specific cells did not enhance suppression of viral replication.
长期以来，人们一直推测，尽管 CD8 淋巴细胞能够抑制人类免疫缺陷病毒（HIV-1）的复制，但一旦形成病毒库，就不太可能被清除。我们之前的研究表明，用猴免疫缺陷病毒（SHIV）DNA 疫苗对食蟹猴进行共同免疫，可诱导强烈的细胞免疫反应，从而抑制病毒复制。我们进一步证明白细胞介素（IL）-12 可显著增强疫苗特异性 CD8 淋巴细胞反应。在本研究中，食蟹猴用携带白细胞介素（IL）-12 的 SHIV DNA 疫苗进行了接种。然后，用 SHIV89.6p 对这些猴子进行了攻毒。免疫接种和病毒攻毒 2 年后，我们短暂地耗尽了 CD8（+）T 细胞。血浆病毒载量增加，这表明 CD8（+）T 细胞在病毒抑制中起着核心作用，但不能清除病毒库。此外，在本研究中，我们发现产生 IFN-γ的疫苗特异性细胞数量增加并没有增强对病毒复制的抑制作用。
