Generation of gp96SIVIg/TNFSF13 and gp96SIVIg/TNFSF15 vaccinesVaccines

gp96SIVIg/TNFSF13 和 gp96SIVIg/TNFSF15 疫苗的生成疫苗

基本信息

批准号：
8198209
负责人：
ECKHARD R PODACK
金额：
$ 32.98万
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：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8198209
关键词：
Adjuvant Antibodies Antigens CD8B1 gene Capsid Cell membrane Cells Cervix Uteri Chimeric Proteins Client Collaborations Complementary DNA Contracts Disease Endocytosis Engineering Gagging Gene Expression Generations Genes Genital system Genomics HIV HIV Envelope Protein gp120 HIV Infections Heat shock proteins Heterosexuals Human Human Papilloma Virus Vaccine Human Papillomavirus Human papillomavirus 16 Immune response Immune system Immunohistochemistry In Situ Hybridization Infection Knowledge Lamina Propria Macaca Membrane Proteins Molecular Chaperones Molecular Profiling Mucosal Immune Responses Mucosal Immunity Mucous Membrane Mucous body substance Mus Pathology Pathway interactions Peptides Phosphoproteins Plasmids Proteins Proteomics Rectum Regimen Route SIV SIV Vaccines Signal Pathway Signal Transduction Systems Biology T cell response T-Lymphocyte TLR2 gene TLR4 gene TNFSF15 gene United States National Institutes of Health Vaccination Vaccines Vagina Viral Woman base cell injury cell mediated immune response immune activation improved intraepithelial jejunum keratinocyte men mucosal vaccine novel particle prevent rectal response retanef tool transmission process vector

项目摘要

Protection from HIV and SIV requires mucosal immunity. We have developed unconventional and safe vaccines based on the delivery of SIV antigens via heat shock protein-chaperone gp96 or by HPV pseudovirion particles. We have already established that the two vaccines generate powerful vaginal and rectal immune responses that are polyepitope specific and multifunctional and generate antigen specific antibody and T cell responses, including CD8 CTL. We hypothesize and will determine that the vaccines will modify the response to vaginal SIV challenge with the effect of protecting macaques from SIV disease. We further hypothesize that by analyzing simultaneously (i) mucosal barrier function of the cervicovaginal mucus, (ii) innate and (iii) adaptive immune responses in vagina/cervix, (iv) gene expression profiles, proteomic (v) phosphoproteins and (vi) plasma membrane proteins, we will be able with the tools of systems biology identify transcriptional and signaling pathways that correlate with protection from vaginal SIV challenge. Finally, since the two vaccine approaches are distinct molecularly and mechanistically, we hypothesize that they will be synergistic if combined in a prime boost strategy and additionally combined with gp120 protein and adjuvant. This will be determined. While we are optimistic that the vaccines singly or in combination will be protective against vaginal SIV challenge, our studies also will provide the information how to further improve our vaccine approach, if even stronger protection is required.

免受艾滋病毒和SIV的保护需要粘膜免疫。我们已经发展了非常规且安全基于通过热休克蛋白 - 伴侣GP96或HPV递送SIV抗原的疫苗伪情节颗粒。我们已经确定，两种疫苗会产生强大的阴道和直肠免疫反应是多题材特异性且多功能的，并产生抗原特异性抗体和T细胞反应，包括CD8 CTL。我们假设并确定疫苗将修改对阴道SIV挑战的反应，以保护猕猴免受SIV疾病的影响。我们进一步假设，通过同时分析子宫颈阴道的粘膜屏障功能粘液，（ii）固有和（iii）阴道/子宫颈的自适应免疫反应，（iv）基因表达谱，，蛋白质组学（V）磷蛋白和（VI）质膜蛋白，我们将能够使用系统的工具生物学识别与阴道SIV保护相关的转录和信号通路挑战。最后，由于两种疫苗方法在分子和机械上都是不同的，我们假设如果将它们合并为主要的提升策略，并与 GP120蛋白质和辅助。这将被确定。当我们乐观地认为疫苗单独或在结合将对阴道SIV挑战进行保护，我们的研究还将提供信息如何进一步改善我们的疫苗方法，即使需要更强的保护。