CD40L adjuvanted clade C DNA and MVA HIV vaccines

CD40L 佐剂 C 分支 DNA 和 MVA HIV 疫苗

• 批准号: 8821574
• 负责人: Rama Rao Amara
• 金额: $ 197.33万
• 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/8821574
• 关键词: Acquired Immunodeficiency Syndrome; Adjuvant; Africa; Africa South of the Sahara; Antibodies; Antibody Response; 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; phase I trial; 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）：在过去的三十年里，开发一种有效的 HIV-1 疫苗一直是一个难以实现的目标。因此，遏制这种病毒在全球范围内引发的流行病成为一项重大挑战。泰国 RV44 功效试验的结果激发了 HIV 疫苗开发的新高度，并有力支持了疫苗接种方法的开发，这些方法可提高抗 HIV Env 抗体的滴度和功能质量，从而可能显着增强对 HIV 的保护。 该计划的总体目标是开发新的疫苗接种方法，不仅增强抗 HIV 细胞和体液免疫的强度，而且增强其功能质量。具体来说，我们建议结合埃默里大学最近开发的两种新的疫苗接种方法，这两种方法在恒河猴中显示出巨大的前景。第一种方法使用 CD40L，这是一种树突状细胞 (DC) 和 B 细胞的共刺激分子，在 HIV VLP 表面表达，作为遗传佐剂，用于增强 HIV 特异性细胞和体液免疫的强度和功能质量，从而增强对 SIV 感染的保护。第二种方法使用缺乏 4 个免疫调节基因 (MVAA4) 的新 MVA 作为疫苗载体，该载体显示恒河猴的 HIV 特异性细胞和体液免疫程度显着增加。在这个项目中，我们希望将这两种新的互补方法结合起来，开发一种新的艾滋病毒疫苗接种策略。该计划将由埃默里大学（Amara、Mulligan、Derdeyn 和 Velu 博士）、NIH（Moss 博士）、国际艾滋病疫苗倡议（lAVI；Dean 博士）、沃尔特·里德陆军研究所（WRAIR；Michael 博士）、路易斯安那州立大学（LSU；Kozlowski 博士）和 CDC（Garber 博士）的科学家共同努力。 该计划有3个项目和两个核心。拟议的计划建立在我们的 DNA 和 MVA 疫苗在临床前和临床环境中的丰富经验以及临床前模型中新疫苗的强大初步数据的基础上。该计划的成功完成将导致两种新疫苗产品和一种新型艾滋病毒疫苗的临床开发。