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（申请人提供）：需要一种安全有效的疫苗来控制由人类免疫缺陷病毒（HIV）引起的全球艾滋病流行。水痘-带状疱疹病毒（VZVOka）减毒活疫苗是表达其他病原体的外源抗原的有吸引力的疫苗载体。它被证明是安全的，目前被许可用于儿童和成人。猴水痘病毒（SVV）与VZV密切相关，在非人灵长类动物中引起一种自然的水痘样疾病。我们的长期目标是建立一种新的儿科，活的，减毒的重组水痘-艾滋病疫苗方案，以产生病毒特异性免疫的婴儿和幼儿，在他们的免疫系统非常活跃的时候，以及在性成熟之前，以保护他们免受粘膜HIV感染。我们的假设是，双重鼻内和皮下rSVV-SIV初免和电穿孔SIV DNA加强，在SIV攻击前延长休息，将1）是安全的，2）促进最大的病毒特异性免疫应答，3）提供针对粘膜SIV攻击的保护而不增加SIV易感性，和4）预先存在的SVV免疫将不会减少疫苗诱导的免疫应答。这一假设建立在我们的发现的特异性免疫应答和显着降低血浆SIV负荷后，rSVV-SIV免疫和SIV静脉内攻击。SIV DNA的体内电穿孔已显示刺激免疫应答，包括粘膜免疫，并显著减少SIV攻击后的SIV病毒血症。本提案将利用猴水痘和儿科艾滋病恒河猴模型，在SVV初治和SVV血清阳性的婴儿恒河猴中测试rSVV-SIV Prime、SIV DNA Boost免疫策略和粘膜SIV攻毒，以确定免疫途径、病毒特异性免疫应答、靶向表位、既存SVV免疫的影响以及对SIV粘膜攻毒的保护。我们的目标是>80%的感染保护可能更好地预测人体试验结果。这样的结果将加速相应的rVZV-HIV疫苗的开发，简化审批和随后的临床人体试验。一种安全有效的儿童rVZV-HIV疫苗将是一项重大的艾滋病预防战略，特别是对世界上艾滋病流行地区的儿童。