A Lassa Vaccine in primates with AIDS

用于患有艾滋病的灵长类动物的拉沙疫苗

• 批准号: 7646424
• 负责人: Maria S. Salvato
• 金额: $ 22.5万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-12-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7646424
• 关键词: Acquired Immunodeficiency Syndrome; Address; Aerosols; Africa; Africa South of the Sahara; Arenavirus; Arenavirus Infections; Attenuated; Attenuated Vaccines; Benign; Biological Warfare; Categories; Cavia; Cessation of life; Development Plans; Disease; Family; Goals; HIV; HIV vaccine; Health; Immune; Immune response; Immunity; Incidence; Infection; Lassa Fever; Lassa fever virus; Left; Life; Lymphocytic choriomeningitis virus; Macaca; Modeling; Monkeys; Organ Transplantation; Performance; Persons; Primates; Public Health; Rodent; SIV; Safety; Scourge; Simulate; Testing; Touch sensation; Transplant Recipients; Transplanted tissue; Vaccination; Vaccine Antigen; Vaccines; Virulent; Virus; biothreat; effective therapy; immunogenic; immunosuppressed; man; pathogen; programs; public health relevance; research study; vaccine development; vaccine evaluation

DESCRIPTION (provided by applicant): A Lassa vaccine in primates with AIDS Lassa fever virus is a rodent-borne scourge in West Africa and, less has been classified as a Category A biothreat in the US because of its lethality and aerosol-transmissibility. Efforts to control Lassa fever focus largely on vaccine development, because the disease course is exceptionally rapid and effective therapies are usually too late. We developed a candidate attenuated vaccine, MOP/LAS that is a reassortant between Lassa Josiah strain and the avirulent Mopeia strain. It is an attenuated, infectious vaccine that protects guinea pigs from lethal challenge with Lassa fever virus. As part of our vaccine development plan, we want to understand the interactions between this Lassa fever vaccine and HIV, since these pathogens are endemic in the same regions of sub-Saharan Africa. In this study, we employ the SIV/macaque model for AIDS to simulate the immune-suppressed state of persons living with HIV. Our goal is to determine whether an attenuated arenavirus vaccine could be safe and immunogenic in macaques with SIV disease. These studies will touch on a broader issue that arose recently when 3 organ transplant recipients died due to LCMV infection of the transplanted tissue, thus raising the possibility that an ordinarily benign arenavirus can become virulent in immune-suppressed hosts. Our hypothesis is that an attenuated vaccine strain will not become more virulent in an AIDS- immunosupressed host. We propose to test this hypothesis in SIV-infected monkeys remaining from completed AIDS studies, and we will use criteria for virulent and benign arenavirus infections developed in our previous macaque studies. Our specific aims are to: 1) Test the hypothesis that an attenuated Lassa vaccine (MOP/LAS) will remain attenuated in macaques where immunity is suppressed during SIV-acquired immunodeficiency syndrome (AIDS). 2) Test the hypothesis that AIDS monkeys given an attenuated arenavirus will develop robust immune responses to vaccine antigens. Our long-term goal is to deliver a vaccine against Lassa fever to West Africa, and to derive from these studies basic information on immune responses to vaccination in the context of AIDS. A successful Lassa fever vaccine should be safe and available to persons with HIV, and Lassa vaccination programs must anticipate any effect of endemic HIV on vaccine performance. PUBLIC HEALTH RELEVANCE: A Lassa vaccine in primates with AIDS Lassa fever virus causes a deadly disease in man and is a serious public health threat in West Africa. Though it can potentially be used in biowarfare, this family of viruses are not a serious health threat in the US (except for the rare incidence of lethal contamination for transplant patients). We developed a vaccine that successfully protected guinea pigs. We have the chance to test the vaccine in monkeys left over from an AIDS experiment, and this test will address the safety of our vaccines in people with AIDS. This is an important question since the Lassa endemic region of West Africa also has a high incidence of AIDS.

描述（由申请人提供）：具有艾滋病LASSA发烧病毒的灵长类动物中的LASSA疫苗是西非的啮齿动物传播祸害，由于其致死性和气雾剂 - 可承受性，因此在美国被归类为A类生物疗法。控制LASSA发烧的努力主要集中在疫苗开发上，因为疾病病程非常快速有效地疗法通常为时已晚。我们开发了一种候选疫苗，MOP/LAS，它是Lassa Josiah菌株和无毒的Mopeia菌株之间的重新成型。这是一种衰减的传染性疫苗，可保护豚鼠免受Lassa Fever病毒的致命挑战。作为我们的疫苗开发计划的一部分，我们希望了解这种LASSA热疫苗和艾滋病毒之间的相互作用，因为这些病原体在撒哈拉以南非洲的同一地区是特有的。在这项研究中，我们采用SIV/猕猴模型来模拟艾滋病毒感染者的免疫抑制状态。我们的目标是确定衰减的体育症病毒疫苗是否可以安全且具有SIV疾病猕猴的免疫原性。这些研究将涉及一个更广泛的问题，该问题最近由于3个器官移植受者而死于移植组织的LCMV感染，从而提高了通常良性良性体育症病毒在免疫抑制的宿主中有害的可能性。我们的假设是，衰减的疫苗菌株不会在AIDS-免疫服用宿主中变得更加毒。我们建议在完整的艾滋病研究中剩下的SIV感染的猴子中检验这一假设，我们将使用标准用于我们以前的猕猴研究中开发的毒和良性体育症病毒感染。我们的具体目的是：1）检验以下假设：减毒的LASSA疫苗（MOP/LAS）将在猕猴中衰减，在猕猴中，在SIV获得的免疫缺陷综合征（AIDS）期间，免疫力受到抑制。 2）检验以下假设：艾滋病猴子给予衰减的体育症病毒将对疫苗抗原产生强大的免疫反应。我们的长期目标是向西非开出针对LASSA热的疫苗，并从这些研究中得出有关在艾滋病背景下对疫苗接种免疫反应的基本信息。成功的LASSA热疫苗应该是安全的，并可能对艾滋病毒患者使用，而LASSA疫苗接种计划必须预期流行艾滋病毒对疫苗性能的任何影响。公共卫生相关性：具有艾滋病LASSA发烧病毒的灵长类动物中的LASSA疫苗会导致人类致命的疾病，并且在西非是严重的公共卫生威胁。尽管它可能在生物乳化中使用，但在美国，这种病毒家族并不是严重的健康威胁（除了对移植患者的致命污染罕见发生率外）。我们开发了一种成功保护豚鼠的疫苗。我们有机会在艾滋病实验中剩下的猴子中测试疫苗，该测试将解决我们艾滋病患者疫苗的安全性。这是一个重要的问题，因为西非的Lassa流行地区也有很高的艾滋病发生率。