Effect of immunization route and prior immunity for a live attenuated varicella AIDS vaccine

水痘艾滋病减毒活疫苗免疫途径和既往免疫效果的影响

• 批准号: 9141565
• 负责人: VICKI L TRAINA-DORGE
• 金额: $ 83.52万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9141565
• 关键词: AIDS Vaccines; AIDS prevention; Accounting; Acquired Immunodeficiency Syndrome; Adult; Age; Antibodies; Antibody Avidity; Antigens; Area; Attenuated; Attenuated Live Virus Vaccine; B-Lymphocytes; Biological; Blood; CD4 Positive T Lymphocytes; CD8B1 gene; Cells; Chickenpox; Chickenpox Vaccine; Child; Childhood; Clinical; Clinical Trials; Cytomegalovirus; DNA; DNA Vaccines; Development; Disease; Disease Progression; Disease model; Dose; Electroporation; Epidemic; Epitopes; Failure; Generations; Goals; HIV; HIV vaccine; HIV-2; Herpes zoster disease; Herpesviridae; Herpesvirus Type 3; Human; Immune; Immune response; Immune system; Immunity; Immunization; Infant; Infection; Intramuscular; Intravenous; Knowledge; Licensing; Life; Macaca mulatta; Maps; Measures; Memory; Mission; Modeling; Mucosal Immune Responses; Mucosal Immunity; Nose; Outcome; Peripheral; Persons; Plasma; Population; Preclinical Testing; Predisposition; Prevention strategy; Protocols documentation; Public Health; Recombinants; Research; Rest; Risk; Route; SIV; SIV Vaccines; Safety; Serum; Subcutaneous Injections; System; T cell response; T-Cell Proliferation; T-Lymphocyte; Testing; Time; Translations; United States National Institutes of Health; VZV vaccine; Vaccination; Vaccines; Viral Load result; Viremia; Virus; Virus Diseases; cytokine; disability; immunosuppressed; in vivo; lymph nodes; neutralizing antibody; nonhuman primate; novel; pathogen; pediatric AIDS; prevent; prototype; public health relevance; response; seropositive; simian virus; subcutaneous; success; vaccine efficacy; vaccine evaluation; vaccine trial; vector; vector vaccine

 DESCRIPTION (provided by applicant): A safe and effective vaccine is needed to control the worldwide AIDS epidemic caused by the human immunodeficiency virus (HIV). The live, attenuated varicella zoster virus (VZVOka) vaccine is an attractive vaccine vector to express foreign antigens of other pathogens. It is proven safe and currently licensed for children and adults. The simian varicella virus (SVV), closely related to VZV, causes a natural, varicella-like disease in nonhuman primates. Our long term goal is to establish a novel pediatric, live, attenuated recombinant varicella-AIDS vaccine protocol to produce virus specific immunity in infants and young children, at a time when their immune systems are extremely active and well before sexual maturity to protect them against mucosal HIV infection. Our hypothesis is that a dual intranasal and subcutaneous rSVV-SIV Prime and electroporated SIV DNA Boost, with extended rest prior to SIV challenge will 1) be safe, 2) promote maximum virus specific immune responses 3) provide protection against mucosal SIV challenge without increasing SIV susceptibility and 4) preexisting SVV immunity will not diminish the vaccine induced immune responses. This hypothesis builds on our findings of specific immune responses and significantly reduced plasma SIV load following rSVV-SIV immunization and SIV intravenous challenge. In vivo electroporation of SIV DNA has been shown to stimulate immune responses, including mucosal immunity and significantly reduce SIV viremia following SIV challenge. This proposal will utilize the simian varicella and pediatric AIDS rhesus models to test the rSVV-SIV Prime, SIV DNA Boost immunization strategy and mucosal SIV challenge in SVV naïve and SVV seropositive infant rhesus to define immunization route, virus specific immune responses, targeted epitopes, effects of preexisting SVV immunity, and protection against an SIV mucosal challenge. Our goal of >80% protection from infection may be better predictive of human trial outcomes. Such outcomes would hasten development of a counterpart rVZV-HIV vaccine, streamlined approvals and subsequent clinical human trials. A safe and effective pediatric rVZV-HIV vaccine would be a monumental AIDS prevention strategy, especially for children in areas of the world with endemic HIV infection.

 描述（由适用提供）：需要一种安全有效的疫苗来控制人类免疫缺陷病毒（HIV）引起的全球艾滋病流行。活的，减毒的水痘带状疱疹病毒（VZVOKA）疫苗是一种有吸引力的疫苗载体，可表达其他病原体的外抗原。它被证明是安全的，目前已获得儿童和成人的许可。与VZV接近相关的猿猴水痘病毒（SVV）在非人类原发性中引起天然的水痘样疾病。我们的长期目标是建立一种新型的儿科，活，减弱的重组毒素艾滋病疫苗方案，以在婴儿和幼儿中产生特定的病毒免疫学，当时他们的免疫学系统非常活跃并且在性成熟之前非常活跃，以保护他们免受粘膜HIV感染的侵害。我们的假设是，双重鼻内和皮下RSVV-SIV素数和电穿孔的SIV DNA提升，在SIV挑战之前进行延长的休息时间延长。该假设建立在我们对特定免疫反应的发现，并在RSVV-SIV免疫抑制和SIV静脉内攻击后显着降低了血浆SIV载荷。 SIV DNA的体内电穿孔已被证明可刺激免疫调查，包括粘膜免疫学，并在SIV攻击后显着降低SIV病毒血症。 This proposal will utilize the simian varicella and pediatric AIDS rhesus models to test the rSVV-SIV Prime, SIV DNA Boost immunosuppression strategy and mucosal SIV challenge in SVV naïve and SVV serapositive Infant rhesus to define immunosuppression route, virus specific immunoresponses, targeted epitopes, effects of preexisting SVV immunology, and防止SIV粘膜挑战。我们对感染的80％保护的目标可能可以更好地预测人类试验结果。这样的结果将开发对应物RVZV-HIV疫苗，简化批准和随后的临床人类试验。一种安全有效的小儿RVZV-HIV疫苗将是一种巨大的艾滋病预防策略，尤其是对于世界上艾滋病毒感染的世界儿童而言。