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：
7228344
负责人：
Geoffrey William Stone
金额：
$ 16.2万
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/7228344
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 Class 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 Numbers Production Property Public Health Range 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 study 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奖项项目旨在支持PI向成为学术机构的独立研究人员的过渡。 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。他的最新工作表明，基于小鼠的HIV DNA疫苗的可溶性，多聚体CD40L和GITRL分子佐剂的强烈作用。利用该K22奖的支持，PI将这些分子佐剂转移到针对HIV的腺病毒疫苗中，以使这些有希望的疫苗更加强。为此，提出了四个具体目标：（1）准备含有HIV GAG的腺病毒载体以及新型的可溶性多聚体CD40L或GITRL。（2）确定这些分子辅助性腺病毒是否在体外是树突状细胞的有效活化剂。（3）确定这些TNFSF的腺病毒疫苗是否比其非辅助的腺病毒疫苗会引起更强，更广泛，更持久的反应。（4）确定这些TNFSF辅助腺病毒疫苗是否能够诱导高水平中和抗腺病毒抗体的小鼠中的免疫反应。这些研究完成后，有望改善在针对艾滋病毒试验中已经测试的腺病毒疫苗。此外，腺病毒疫苗可能会预防许多其他感染，包括生物污染利息的流感，SARS，埃博拉病毒和药物。因此，这种制造更强疫苗的方法（这是PI的科学重点）可能会更好地控制传染病，并具有广泛的公共健康意义。