Cristillo Anthony D, Lisziewicz Julianna, He Leilei, Lori Franco, Galmin Lindsey, Trocio Jeffrey N, Unangst Tami, Whitman Lucia, Hudacik Lauren, Bakare Nyasha, Whitney Stephen, Restrepo Susana, Suschak John, Ferrari Maria Grazi, Chung H K, Kalyanaraman Vaniambadi S, Markham Phillip, Pal Ranajit
Advanced BioScience Laboratories, Inc., 5510 Nicholson Lane, Kensington, MD 20895, USA.
Virology. 2007 Sep 15;366(1):197-211. doi: 10.1016/j.virol.2007.04.012. Epub 2007 May 11.
Topical DNA vaccination (DermaVir) facilitates antigen presentation to naive T cells. DermaVir immunization in mice, using HIV-1 Env and Gag, elicited cellular immune responses. Boosting with HIV-1 gp120 Env and p41 Gag augmented Th1 cytokine levels. Intramuscular DNA administration was less efficient in priming antigen-specific cytokine production and memory T cells. In rhesus macaques, DermaVir immunization induced Gag- and Env-specific Th1 and Th2 cytokines and generation of memory T cells. Boosting of DermaVir-primed serum antibody levels was noted following gp140(SHIV89.6P)/p27(SIV) immunization. Rectal challenge with pathogenic R5-tropic SHIV162P3 resulted in control of plasma viremia (4/5 animals) that was reflected in jejunum, colon and mesenteric lymph nodes. An inverse correlation was found between Gag- and Env-specific central memory T cell responses on the day of challenge and plasma viremia at set point. Overall, the topical DermaVir/protein vaccination yields central memory T cell responses and facilitates control of pathogenic SHIV infection.
局部DNA疫苗接种（DermaVir）有助于将抗原呈递给初始T细胞。在小鼠中使用HIV-1包膜蛋白（Env）和核衣壳蛋白（Gag）进行DermaVir免疫接种，可引发细胞免疫反应。用HIV-1 gp120 Env和p41 Gag加强免疫可提高Th1细胞因子水平。肌肉内注射DNA在启动抗原特异性细胞因子产生和记忆T细胞方面效率较低。在恒河猴中，DermaVir免疫接种可诱导产生Gag和Env特异性的Th1和Th2细胞因子，并产生记忆T细胞。在接种gp140（SHIV89.6P）/p27（SIV）后，观察到DermaVir启动的血清抗体水平有所提高。用致病性R5嗜性SHIV162P3进行直肠攻击后，血浆病毒血症得到控制（4/5只动物），这在空肠、结肠和肠系膜淋巴结中也有所体现。在攻击当天，Gag和Env特异性中央记忆T细胞反应与设定点的血浆病毒血症之间呈负相关。总体而言，局部DermaVir/蛋白疫苗接种可产生中央记忆T细胞反应，并有助于控制致病性SHIV感染。
