Non-peptidic HIV vaccine

描述（由申请人提供）：艾滋病毒引起的艾滋病是一种潜在的致命疾病，目前没有疫苗或治疗方法。在开发有效的艾滋病毒疫苗时，需要克服的障碍包括设计一种策略，使细胞和体液免疫具有足够的a)强度以“挫败病毒复制”，b)广度以应对病毒的非凡遗传多样性。我们的建议特别侧重于提高艾滋病毒疫苗的“免疫强度”。为此，我们开发了高免疫原性的重组减毒李斯特菌疫苗载体和重组乳酸乳球菌疫苗颗粒。这些新的疫苗递送系统的抗原启动和增强引起了显著的t细胞和Ab反应。此外，我们已经证明非肽性磷酸抗原(E)-4-羟基-3-甲基-但-2-烯基焦磷酸（HMBPP）与白细胞介素-2一起刺激淋巴细胞和粘膜室中V32V42 T效应细胞的延长扩张，并增强T细胞和抗体反应。在这里，我们提出了研究，以确定是否可以利用V32V42 t细胞刺激的强免疫佐剂作用来提高HIV疫苗的“免疫强度”。具体来说，我们提出验证我们的假设，即HMBPP/IL-2处理后产生的V32V42 T效应细胞可以很容易地运输到淋巴组织和粘膜，并上调HIV疫苗引发的T细胞和抗体反应的广度和强度，最终增加疫苗对HIV/AIDS的保护作用。因此，我们的主要具体目的是确定HMBPP加IL-2的V32V42 t细胞激活/扩增治疗是否可以增强我们的减毒李斯特菌抗shiv89.6 p的效力？在shiv89.6 p攻击恒河猴中表达HIV-1 Env和SIV gag的prfA*疫苗载体。

DESCRIPTION (provided by applicant): HIV-caused AIDS is a potentially lethal disease with no vaccine or cure available at the moment. The obstacles to overcome when developing an effective HIV vaccine include devising a strategy that would generate cellular and humoral immunity with sufficient a) strength to be 'virus- replication-clobbering' and b) breadth to address the extraordinary genetic diversity of the virus. Our proposal is focused specifically on increasing the 'immunizing strength' of HIV vaccines. For this purpose we have developed highly immunogenic recombinant attenuated Listeria vaccine vectors and recombinant Lactococcus lactis vaccine particles. Antigenic priming and boosting with these new vaccine-delivery systems elicits remarkable T-cell and Ab responses. In addition, we have demonstrated that a nonpeptidic phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) together with interleukin-2 stimulate prolonged expansion of V32V42 T effector cells in the lymphoid and mucosal compartments and enhance 12 T-cell and antibody responses. Here we propose studies to ascertain whether or not the strong immunoadjuvant effect of V32V42 T-cell stimulation can be utilized in increasing the 'immunizing strength' of HIV vaccines. Specifically, we propose to test our hypothesis that V32V42 T effector cells generated after HMBPP/IL-2 treatment can readily traffic to the lymphoid tissues and mucosae and upregulate the breadth and magnitude of HIV vaccine-elicited T-cell and antibody responses and ultimately increase the vaccine's protective effects against HIV/AIDS. Thus, our main specific aim is to determine whether the V32V42 T-cell-activating/expanding treatment with HMBPP plus IL-2 can augment the anti-SHIV89.6P potency of our attenuated Listeria ?actA prfA* vaccine vectors expressing HIV-1 Env and SIV gag in SHIV89.6P-challenged rhesus macaques. PUBLIC HEALTH RELEVANCE: There is no vaccine or cure for HIV/AIDS, which is a potentially lethal disease. The main focus of this application is to test a novel strategy for boosting the capacity of HIV vaccines to induce protective responses against HIV/AIDS. Even partial success may have worldwide beneficial effect.