CD40L and GITRL adjuvants for adenoviral vaccines against HIV

用于 HIV 腺病毒疫苗的 CD40L 和 GITRL 佐剂

基本信息

批准号：
7617016
负责人：
Geoffrey William Stone
金额：
$ 10.8万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-01 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7617016
关键词：
Adenovirus Vector Adenoviruses Adjuvant Animals Antibodies Biochemistry Biological Assay CD80 gene CTL assay Calculi Cell surface Chemokine (C-C Motif) Ligand 4 Communicable Diseases DNA Vaccines Dendritic Cells Dose Future Gagging Generations Goals HIV HIV Antigens HIV vaccine HIV-1 Human I-antigen Immune response Immunity Immunologic Memory Immunology In Vitro Individual Infection Infectious Agent Influenza Institution Interferon Type II Interleukin-12 K22 Award Lead Ligands Macaca Measures Microbiology Modeling Molecular Molecular Biology Mus Production Property Public Health Research Research Personnel Rest Serotyping Severe Acute Respiratory Syndrome Solutions Staining method Stains T memory cell TNF gene TNFRSF5 gene TNFSF5 gene Testing Time Vaccinated Vaccination Vaccines Vaccinia Variant Viral Virus Work base biodefense chemokine cytokine design enzyme linked immunospot assay gag Gene Products human subject improved in vivo interest monocyte novel particle research study response vector vector vaccine

项目摘要

DESCRIPTION (provided by applicant): This K22 Award project is designed to support the PI's transition to becoming an independent researcher at an academic institution. The PI has prepared for this research through studies in molecular biology biochemistry, microbiology, and immunology. His most recent work has shown the strong effects of soluble, multimeric CD40L- and GITRL-based molecular adjuvants on HIV DNA vaccines in mice. Using support from this K22 award, the PI would move these molecular adjuvants into adenoviral vaccines against HIV, in order to make these promising vaccines even stronger. To this end, four Specific Aims are proposed: (1) To prepare adenoviral vectors containing HIV Gag along with novel soluble multimeric CD40L or GITRL. (2) To determine if these molecularly adjuvanted adenoviruses are effective activators of dendritic cells in vitro. (3) To determine if these TNFSF-adjuvanted adenoviral vaccines induce stronger, broader, and longer-lasting responses than do their unadjuvanted counterparts. (4) To determine if these TNFSF-adjuvanted adenoviral vaccines are capable of inducing immune responses in mice that have high levels of neutralizing anti-adenoviral antibodies. These studies, when complete, promise to improve adenoviral vaccines that are already being tested in human trials against HIV. In addition, adenoviral vaccines may protect against many other infections, including influenza, SARS, Ebola, and agents of biodefense interest. Thus, this approach toward making stronger vaccines, which is the PI's scientific focus, could lead to better control of infectious diseases and has broad public health significance.

描述（由申请人提供）：该 K22 奖项目旨在支持 PI 过渡为学术机构的独立研究员。 PI 通过分子生物学、生物化学、微生物学和免疫学的研究为这项研究做好了准备。他最近的研究表明，基于可溶性多聚体 CD40L 和 GITRL 的分子佐剂对小鼠 HIV DNA 疫苗具有强大的作用。利用 K22 奖项的支持，PI 将把这些分子佐剂转移到抗 HIV 的腺病毒疫苗中，以使这些有前途的疫苗更加强大。为此，提出了四个具体目标：（1）制备含有HIV Gag以及新型可溶性多聚体CD40L或GITRL的腺病毒载体。 (2) 确定这些分子佐剂腺病毒是否是体外树突状细胞的有效激活剂。 (3) 确定这些 TNFSF 佐剂腺病毒疫苗是否比未佐剂的腺病毒疫苗诱导更强、更广泛和更持久的反应。 (4) 确定这些 TNFSF 佐剂的腺病毒疫苗是否能够在具有高水平中和性抗腺病毒抗体的小鼠中诱导免疫反应。这些研究完成后，有望改进已经在人体试验中针对艾滋病毒进行测试的腺病毒疫苗。此外，腺病毒疫苗可以预防许多其他感染，包括流感、SARS、埃博拉和生物防御药物。因此，这种制造更强效疫苗的方法是 PI 的科学重点，可以更好地控制传染病，并具有广泛的公共卫生意义。