CD40L adjuvanted clade C DNA and MVA HIV vaccines

CD40L 佐剂 C 分支 DNA 和 MVA HIV 疫苗

• 批准号: 8637403
• 负责人: Rama Rao Amara
• 金额: $ 200万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-15 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8637403
• 关键词: Acquired Immunodeficiency Syndrome; Adjuvant; Africa; Africa South of the Sahara; Antibodies; Antibody Formation; Antigens; Asia; B-Lymphocytes; Binding; Biological Assay; Cause of Death; Cellular Immunity; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Trials; Collaborations; Communication; Cyclic GMP; DNA; DNA Vaccines; Data; Dendritic Cells; Developing Countries; Development; Epidemic; Evaluation; Future; Genes; Genetic; Goals; Growth; HIV; HIV Infections; HIV vaccine; HIV-1; Human; Humoral Immunities; Immune; Immune response; Immunity; Immunization; Individual; Infection; Infection prevention; International; Lead; Leadership; Life; Louisiana; Macaca; Macaca mulatta; Measures; Mediating; Membrane; Modeling; Modified Vaccinia Virus Ankara; Mosses; National Institute of Allergy and Infectious Disease; Persons; Phase; Phase I Clinical Trials; Pre-Clinical Model; Property; Proteins; Protocols documentation; Recombinants; Regulatory Affairs; Research; Research Institute; SIV; Safety; Sampling; Scientist; Specificity; Surface; TNFSF5 gene; Testing; Thailand; United States National Institutes of Health; Universities; Vaccinated; Vaccination; Vaccines; Viral; Viral Vector; Virus; Virus-like particle; efficacy trial; experience; gp160; immunogenicity; improved; in vivo; novel; novel vaccines; pre-clinical; preclinical study; prevent; programs; public health relevance; research clinical testing; safety testing; simian human immunodeficiency virus; stem; vaccination strategy; vaccine evaluation; vector; vector vaccine

DESCRIPTION (provided by applicant): Development of an effective vaccine against HIV-1 has been an elusive goal for the past three decades. As a result it has been a major challenge to stem the tide of the epidemic caused by this virus globally. The results of the RV44 efficacy trial in Thailand have spurred a new level of excitement for the development of HIV vaccine and strongly support the development of vaccination approaches that enhance the titer and functional quality of anti-HIV Env antibody that may significantly enhance protection against HIV. The overall goal of this program is to develop novel vaccination approaches that not only enhance the magnitude but also enhance the functional quality of anti-HIV cellular and humoral immunity. Specifically, we propose to combine two new vaccination approaches developed recently at Emory University that showed great promise in rhesus macaques. The first approach uses CD40L, a co-stimulatory molecule for dendritic cells (DC) and B cells, expressed on the surface of HIV VLPs as a genetic adjuvant for enhancing the magnitude and functional quality of HIV-specific cellular and humoral immunity leading to enhanced protection from acquisition of SIV infection. The second approach uses a new MVA that lacks 4 immune modulatory genes (MVAA4) as a vaccine vector that showed a significant increase in the magnitude of HIV-specific cellular and humoral immunity in rhesus macaques. In this program, we hope to combine these two new complementary approaches to develop a novel vaccination strategy against HIV. This program will be a collaborative effort between scientists at the Emory University (Drs. Amara, Mulligan, Derdeyn, and Velu), NIH (Dr. Moss), International AIDS Vaccine Initiative (lAVI; Dr. Dean), Walter Reed Army Institute of Research (WRAIR; Dr. Michael), Louisiana State University (LSU; Dr. Kozlowski) and CDC (Dr. Garber). This Program has 3 projects and two cores. The proposed program builds upon the enormous experience with our DNA and MVA vaccines in the preclinical and clinical settings and strong preliminary data with the new vaccines in the preclinical model. Successful completion of the program will result in the clinical development of two new vaccine products and a novel HIV vaccine.

描述（由申请人提供）：在过去的三十年中，开发针对HIV-1的有效疫苗一直是一个难以捉摸的目标。结果，阻止该病毒在全球范围内引起的流行病的潮流是一个重大挑战。泰国RV44疗效试验的结果刺激了新的兴奋水平，以开发HIV疫苗，并强烈支持疫苗接种方法的开发，从而增强了抗HIV ENK抗体的滴度和功能质量，这些抗体可能会显着增强对HIV的保护。 该计划的总体目标是开发新型的疫苗接种方法，不仅可以增强幅度，还可以提高抗HIV细胞和体液免疫的功能质量。具体来说，我们建议结合最近在埃默里大学开发的两种新的疫苗接种方法，这些方法在恒河猕猴中表现出了很大的希望。第一种方法使用在HIV VLPs表面表达的树突状细胞（DC）和B细胞的共刺激分子CD40L作为遗传佐剂，以增强HIV特异性细胞和体液免疫力的幅度和功能质量，从而增强了对Siv Invection的获得的增强保护。第二种方法使用一种新的MVA，该MVA缺乏4个免疫调节基因（MVAA4）作为一种疫苗载体，该疫苗载体显示恒河猴中HIV特异性细胞和体液免疫的大小显着增加。在该计划中，我们希望结合这两种新的补充方法，以制定针对艾滋病毒的新型疫苗接种策略。该计划将是埃默里大学（Emory University）（Amara博士，Mulligan，Derdeyn和Velu博士），NIH（MOSS博士），国际艾滋病疫苗倡议（Lavi; Dean; Dean），沃尔特·里德·里德（Dean），沃尔特·里德（Dean）博士，麦克尔（Walter Reed）陆军研究所（士兵;迈克尔（Michael），路易斯安那州立大学（Louisiana State University）（lsu; kozlowski; ccdclosski）。 该计划有3个项目和两个核心。拟议的程序基于临床前和临床环境中的DNA和MVA疫苗的巨大体验，并在临床前模型中使用新疫苗进行了强大的初步数据。该计划的成功完成将导致两种新疫苗产品和一种新型的HIV疫苗的临床开发。