Validation of a new VL vaccine candidate in dogs that significantly protects mice

在狗身上验证一种新的 VL 候选疫苗可显着保护小鼠

• 批准号: 8391037
• 负责人: Claudia Abeijon
• 金额: $ 30万
• 依托单位: DETECTOGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-23 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8391037
• 关键词: Adjuvant; Animal Model; Animals; Antigens; BCG Vaccine; Blood Circulation; Bodily secretions; Bone Marrow; Canis familiaris; Clinical; Code; Communicable Diseases; Development; Disease; Disease model; Evaluation; Foundations; Future; Genes; Genome; Goals; Gold; High Pressure Liquid Chromatography; Host Defense; Human; Immunity; Immunization; Incidence; Iron Superoxide Dismutase; Leishmania donovani; Leishmania infantum; Lesion; Liquid substance; Liver; Lung; Mass Spectrum Analysis; Modeling; Morbidity - disease rate; Mus; Mycobacterium tuberculosis; Organ; Organism; Parasites; Patients; Peptides; Pharmaceutical Preparations; Phase; Proteins; Pulmonary Tuberculosis; Recombinant Proteins; Recombinants; Research; Research Project Grants; Sampling; Small Business Innovation Research Grant; Source; Spleen; Testing; Translations; Tuberculosis; Urinary tract; Urine; Vaccines; Validation; Virulent; Visceral Leishmaniasis; base; immunogenicity; in vivo; microbial; microorganism antigen; mortality; novel; nuclear transport factor 2; pathogen; prevent; programs; research clinical testing; response; vaccine candidate

DESCRIPTION (provided by applicant): The long-term goal of this research program is to validate in dogs a candidate vaccine against visceral leishmaniasis (VL) for evaluation in future clinical evaluations. We have recently described a powerful and reliable antigen discovery strategy to directly identify microbial vaccine candidate antigens in human bodily secretions. We combined RP-HPLC and mass spectrometry and categorized three distinct Leishmania infantum proteins presumably produced in parasite infected organs (liver/spleen/bone marrow) and excreted in the urine of patients with VL. The hypothesis underlying these studies was that microbial antigens found in vivo in the bodily fluids of the host are potentially effective vaccine candidate molecules because they represent microbial molecules abundantly produced in vivo that can be directly associated with the host defenses. The genes coding for these L. infantum proteins found in the patients' urine have been cloned, and the purified recombinant molecules have been obtained. Mice immunized with these proteins mixed with the adjuvant MPLA-SE developed robust Th1 response. Importantly one of these proteins induced strong protection in these animals after challenged with virulent L. infantum. The next and pragmatic challenge in the clinical translation of these findings is to expand these initial developmental studies and show that this novel molecule induces protective immunity in dogs, which are the ultimate animal model to test vaccine candidates for both human and canine VL. PUBLIC HEALTH RELEVANCE: Visceral Leishmaniasis (VL) remains a major infectious cause of morbidity and mortality worldwide in both humans and dogs. The incidence of the disease remains high and is increasing in many parts of the world. There is no efficacious vaccine to prevent VL and treatment of this disease is difficult and the drugs are toxic. The present project proposes to validate in the dog model of the disease a novel and promising vaccine candidate for assessment in future clinical evaluations against both human and canine VL.

描述（由申请人提供）：本研究项目的长期目标是在狗身上验证一种抗内脏利什曼病（VL）的候选疫苗，以便在未来的临床评估中进行评估。我们最近描述了一种强大而可靠的抗原发现策略，可以直接识别人体分泌物中的微生物疫苗候选抗原。我们结合RP-HPLC和质谱分析，对三种不同的婴儿利什曼原虫蛋白进行了分类，这些蛋白可能产生于寄生虫感染的器官（肝脏/脾脏/骨髓），并从VL患者的尿液中排出。这些研究背后的假设是，在宿主体液中发现的微生物抗原可能是有效的疫苗