Goletti Delia, Macchia Iole, Leone Pasqualina, Pace Monica, Sernicola Leonardo, Pavone-Cossut Maria Rosaria, Maggiorella Maria Teresa, Cafaro Aurelio, Ensoli Barbara, Titti Fausto
2nd Division of the Health Department, National Institute of Infectious Disease, L. Spallanzani, Rome, Italy.
Med Sci Monit. 2006 Oct;12(10):BR330-40. Epub 2006 Sep 25.
The Delta-nef live attenuated virus vaccine approach offered in the SIV-macaque model the opportunity to identify humoral and cell-mediated immune responses associated with protection against viral infections. In addition, soluble factors different from those related to specific immune responses appear to correlate with the establishment and maintenance of the protective status.
MATERIAL/METHODS: Investigated were: 1) the ability of CD8+ T cells from cynomolgus monkeys vaccinated with SIV Delta-nef and long-term protected against sequential SIVs and SHIV challenges to inhibit in vitro SHIV replication in an acute infection cell system, 2) the ability of cell-free supernatants from CD8+ T cell cultures to inhibit replication of HIV in chronically infected cells, and 3) whether the antiviral activity of CD8+ T cells correlated with IFNgamma production.
Soluble factor(s) secreted by CD8+ T cells from Delta-nef vaccinated monkeys significantly inhibited SHIV replication in an autologous cell system. This effect was not dependent on beta-chemokine secretion and correlated with an increased IFNgamma production. In addition, since supernatants from CD8+ T cells inhibited HIV production in chronically infected monocytic cells, the suppressive activity was not related to the viral strain.
Vaccination with the live attenuated virus induces both a CD8+ T cell-dependent antiviral activity and IFNgamma responses potentially responsible for the protection from challenge with heterologous highly pathogenic SHIV89.6P. It is conceivable that boosting the "natural" along with the antigen-specific immunity is a desirable outcome to improve the protective efficacy of any vaccine approach.
在猴免疫缺陷病毒（SIV）-猕猴模型中采用的Delta-nef减毒活病毒疫苗方法，为识别与预防病毒感染相关的体液免疫和细胞介导免疫反应提供了机会。此外，与特定免疫反应无关的可溶性因子似乎与保护状态的建立和维持相关。
材料/方法：研究了：1）接种SIV Delta-nef并长期免受连续SIV和猿猴-人免疫缺陷病毒（SHIV）攻击的食蟹猴的CD8 + T细胞，在急性感染细胞系统中体外抑制SHIV复制的能力；2）CD8 + T细胞培养物的无细胞上清液抑制HIV在慢性感染细胞中复制的能力；3）CD8 + T细胞的抗病毒活性是否与γ干扰素（IFNγ）的产生相关。
Delta-nef疫苗接种猴的CD8 + T细胞分泌的可溶性因子在自体细胞系统中显著抑制SHIV复制。这种作用不依赖于β趋化因子的分泌，并且与IFNγ产生增加相关。此外，由于CD8 + T细胞的上清液抑制慢性感染单核细胞中的HIV产生，因此抑制活性与病毒株无关。
接种减毒活病毒可诱导CD8 + T细胞依赖性抗病毒活性和IFNγ反应，这可能是免受异源高致病性SHIV89.6P攻击的保护机制。可以想象，增强“天然”免疫以及抗原特异性免疫是提高任何疫苗方法保护效果的理想结果。
