Lucas Carolina G D O, Matassoli Flavio L, Peçanha Ligia M T, Santillo Bruna Tereso, Oliveira Luanda Mara da Silva, Oshiro Telma Miyuki, Marques Ernesto T D A, Oxenius Annette, de Arruda Luciana B
Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;
Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil;
FASEB J. 2016 Aug;30(8):2970-84. doi: 10.1096/fj.201500059. Epub 2016 May 19.
The decline in number and function of T cells is a hallmark of HIV infection, and preservation or restoration of HIV-specific cellular immune response is a major goal of AIDS treatment. Dendritic cells (DCs) play a key role in the initiation and maintenance of the immune response, and their use as a vaccine vehicle is a promising strategy for enhancing vaccine efficacy. We evaluated the potential of DC-mediated immunization with a DNA vaccine consisting of HIV-1-p55gag (gag, group-specific antigen) associated to lysosomal associated protein (LAMP) sequence (LAMP/gag vaccine). Immunization of mice with mouse DCs transfected with LAMP/gag (Lg-mDCs) stimulated more potent B- and T-cell responses than naked DNA or DCs pulsed with inactivated HIV. Anti-Gag antibody levels were sustained for at least 3 mo after immunization, and recall T-cell responses were also strongly detected at this time point. Human DCs transfected with LAMP/gag (Lg-hDCs) were also activated and able to stimulate greater T-cell response than native gag-transfected DCs. Coculture between Lg-hDCs and T lymphocytes obtained from patients with HIV resulted in upregulation of CD38, CD69, HLA-DR, and granzyme B by CD4(+) and CD8(+) T cells, and increased IFN-γ and TNF-α production. These results indicate that the use of LAMP/gag-DC may be an efficient strategy for enhancing immune function in patients with HIV.-Lucas, C. G. D. O., Matassoli, F. L., Peçanha, L. M. T., Santillo, B. T., Oliveira, L. M. D. S., Oshiro, T. M., Marques, E. T. D. A., Jr., Oxenius, A., de Arruda, L. B. Dendritic cells primed with a chimeric plasmid containing HIV-1-gag associated with lysosomal-associated protein-1 (LAMP/gag) is a potential therapeutic vaccine against HIV.
T细胞数量和功能的下降是HIV感染的一个标志，而保存或恢复HIV特异性细胞免疫反应是艾滋病治疗的一个主要目标。树突状细胞（DCs）在免疫反应的启动和维持中起关键作用，将其用作疫苗载体是提高疫苗效力的一个有前景的策略。我们评估了用一种由与溶酶体相关蛋白（LAMP）序列相关的HIV-1-p55gag（gag，群特异性抗原）组成的DNA疫苗进行DC介导免疫的潜力（LAMP/gag疫苗）。用转染了LAMP/gag的小鼠DCs（Lg-mDCs）免疫小鼠，比裸DNA或用灭活HIV脉冲处理的DCs刺激产生更强的B细胞和T细胞反应。免疫后抗Gag抗体水平至少持续3个月，并且在这个时间点也强烈检测到回忆性T细胞反应。用LAMP/gag转染的人DCs（Lg-hDCs）也被激活，并且比天然gag转染的DCs能刺激更强的T细胞反应。Lg-hDCs与从HIV患者获得的T淋巴细胞共培养导致CD4(+)和CD8(+) T细胞上调CD38、CD69、HLA-DR和颗粒酶B，并增加IFN-γ和TNF-α的产生。这些结果表明，使用LAMP/gag-DC可能是增强HIV患者免疫功能的一种有效策略。-卢卡斯，C.G.D.O.，马塔索利，F.L.，佩尚哈，L.M.T.，桑蒂洛，B.T.，奥利维拉，L.M.D.S.，大岛，T.M.，马克斯，E.T.D.A.，小，奥克森纽斯，A.，德阿鲁达，L.B.Dendritic cells primed with a chimeric plasmid containing HIV-1-gag associated with lysosomal-associated protein-1 (LAMP/gag) is a potential therapeutic vaccine against HIV.
