Improved HIV-Adenoviral Vector Vaccine for Re-immunization

用于再免疫的改良 HIV 腺病毒载体疫苗

• 批准号: 7265276
• 负责人: Richard B. Gayle
• 金额: $ 31.29万
• 依托单位: ETUBICS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2009-01-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7265276
• 关键词: Address; Adenovirus Vector; Adenoviruses; Adjuvant; Adverse effects; Adverse reactions; Animal Model; Animals; Antibodies; Antibody Formation; Cell Line; Cell Surface Proteins; Cells; Cellular Immunity; Clinical Data; Clinical Trials; Cloning; Code; Complex; Condition; DNA; Data; Dendritic Cells; Dose; Effectiveness; Ethers; Ethyl Ether; Funding; Gagging; Gene Proteins; Generations; Genes; Goals; Grant; Guanosine Monophosphate; HIV; HIV Infections; HIV vaccine; HIV-1; Head; Housing; Human; Immune; Immune response; Immune system; Immunity; Immunization; Immunologics; Infection; Infection prevention; Infectious Diseases Research; Institution; Kinetics; Knowledge; Licensing; Longevity; Macaca; Mediating; Modeling; Monitor; Mus; National Institute of Allergy and Infectious Disease; Phase; Phase I Clinical Trials; Polymerase; Population; Process; Production; Property; Proteins; Protocols documentation; Range; Reagent; Relative (related person); Reporting; Research; Research Institute; Running; Safety; Shivering; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Specificity; Stimulus; System; Testing; Time; Treatment Protocols; United States Food and Drug Administration; Vaccine Antigen; Vaccine Design; Vaccine Research; Vaccines; Viral; Viral Genes; Virus; base; cell mediated immune response; cost; cost effective; design; env Genes; experience; immunogenic; immunogenicity; improved; nonhuman primate; plasmid DNA; pol genes; pre-clinical; preclinical study; prevent; programs; research study; response; simian human immunodeficiency virus; vaccine delivery; vaccine development; vector; vector vaccine; vector-induced

DESCRIPTION (provided by applicant): The objective of this project is to develop an adenoviral vector vaccine against HIV that is effective in stimulating cell-mediated immunity in animals previously immune to adenovirus The HIV vaccine will be used to protect against infection and to treat the infected. Gag, Pol, and Nef are HIV proteins that have been reported to be useful for vaccine development. Evidence indicates that a broad cell-mediated immune (CMI) response is needed to treat or prevent HIV infection. Adenovirus (Ad) vector vaccines induce CMI responses and have emerged as a leading candidate to be used as a vaccine delivery platform. First Generation Ad vaccines have proven less effective than anticipated and adverse reactions are in question. Furthermore, pre-existing Ad immunity of most humans causes decreased effectiveness. To address these issues, we have developed an advanced Ad based vector that is devoid of early genes E1, E3, and E2B. "E2B-deleted" vectors, with deletions in the polymerase and preterminal protein genes, have an expanded cloning capacity and greatly reduced expression of viral late genes as compared to First Generation Ad vectors. Reduced expression of multiple Ad viral genes is advantageous for vaccine development for reasons such as reduced antigenic competition, greater longevity of expression that provides greater immunologic stimulus and reduced adverse effects. Such advantages are important in the presence of pre-existing Ad immunity since the Ad vector needs to be stealth-like. The Company has exclusive license from the U of M for the new Ad vector system and the E.C7 cell line, which supports vector production. The proposed vaccines based on the new E2B-deleted Ad vector system will carry fused Ad-gag-pol, fused Ad-gag-pol-nef and Clade C env genes. The HIV vaccines will be tested for their potential to induce CMI as a prime and for their re-immunization (boost) potential in Ad-naive and Ad-immune mice. Upon completion of this project we will have developed a new platform for the delivery of HIV vaccines that is effective, safe, stable, cost effective, easy to distribute and use. Our goal is to initiate non-human primate studies in the Phase II SBIR and a Phase I clinical trial using these or like vaccine product within two to three years of funding as pre-clinical data allows.

描述(申请人提供)：该项目的目标是开发一种针对艾滋病毒的腺病毒载体疫苗，该疫苗能够有效地刺激过往对腺病毒免疫的动物的细胞免疫。艾滋病毒疫苗将用于预防感染和治疗感染者。Gag、Pol和Nef是已被报道对疫苗开发有用的HIV蛋白。有证据表明，需要广泛的细胞免疫(CMI)反应来治疗或预防艾滋病毒感染。腺病毒(Ad)载体疫苗诱导CMI反应，已成为疫苗递送平台的首选候选疫苗。第一代Ad疫苗已被证明不如预期的有效，不良反应尚存疑问。此外，大多数人预先存在的Ad免疫会导致效果降低。为了解决这些问题，我们开发了一种先进的基于Ad的载体，该载体缺乏早期基因e1、e3和e2b。与第一代Ad载体相比，e2b缺失的载体具有更大的克隆能力，并且病毒晚期基因的表达大大降低。减少多个Ad病毒基因的表达有利于疫苗的开发，原因包括减少抗原竞争，延长表达寿命，提供更强的免疫刺激，以及减少不良反应。这种优势在存在预先存在的Ad免疫的情况下是重要的，因为Ad载体需要是隐形的。该公司从密歇根大学获得了新的Ad载体系统和支持载体生产的E.C7细胞系的独家许可证。基于新的e2b删除的Ad载体系统的拟议疫苗将携带融合的Ad-Gag-Poll、融合的Ad-gag-polnef和Clade C env基因。将测试HIV疫苗作为主要疫苗诱导CMI的潜力，以及它们在Ad-naive和Ad-免疫小鼠中的再次免疫(Boost)潜力。这个项目完成后，我们将开发一个有效、安全、稳定、成本效益高、易于分发和使用的艾滋病毒疫苗交付新平台。我们的目标是在临床前数据允许的情况下，在资助的两到三年内，启动第二阶段SBIR的非人类灵长类研究和使用这些或类似疫苗产品的第一阶段临床试验。