Generation of gp96SIVIg/TNFSF13 and gp96SIVIg/TNFSF15 vaccinesVaccines

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

• 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
• 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

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.

预防 HIV 和 SIV 需要粘膜免疫。我们开发了非常规且安全的 基于通过热休克蛋白伴侣 gp96 或 HPV 传递 SIV 抗原的疫苗 假病毒颗粒。我们已经确定这两种疫苗可以产生强大的阴道和 直肠免疫反应是多表位特异性和多功能的，并产生抗原特异性 抗体和 T 细胞反应，包括 CD8 CTL。我们假设并将确定疫苗将 改变对阴道 SIV 攻击的反应，具有保护猕猴免受 SIV 疾病的作用。我们 进一步假设，通过同时分析 (i) 宫颈阴道粘膜屏障功能 粘液，(ii) 阴道/子宫颈中的先天性和 (iii) 适应性免疫反应，(iv) 基因表达谱， 蛋白质组 (v) 磷蛋白和 (vi) 质膜蛋白，我们将能够使用系统工具 生物学鉴定与阴道 SIV 保护相关的转录和信号传导途径 挑战。最后，由于这两种疫苗方法在分子和机制上是不同的，我们 假设如果将它们结合在主要增强策略中并另外与 gp120蛋白和佐剂。这将被确定。虽然我们对单独或联合使用疫苗持乐观态度 组合将可以预防阴道 SIV 攻击，我们的研究也将提供信息 如果需要更强的保护，如何进一步改进我们的疫苗方法。