Novel heterologous listeria-adenovirus mucosal vaccine for HIV-1

针对 HIV-1 的新型异源李斯特菌腺病毒粘膜疫苗

基本信息

批准号：
7915872
负责人：
Fred Robert Frankel
金额：
$ 80万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-17 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7915872
关键词：
AIDS Vaccines AIDS vaccine development Absence of pain sensation Acquired Immunodeficiency Syndrome Address Adenovirus Vector Adenoviruses Adjuvant Affect Africa Agreement Alcohols Aliquot Amendment Analgesics Anesthesia procedures Anesthetics Animal Care and Use Committees Animal Experimentation Animal Experiments Animal Feed Animal Housing Animal Model Animal Use Alternatives Animal Welfare Animal Welfare Act Animals Anorexia Antibiotics Antibody Formation Antigens Anus Applications Grants Appointment Area Ascites Attenuated Authorization documentation Award Axilla Back Bacteria Bandage Bathing Behavior Behavior Control Biological Biological Assay Biomedical Research Biopsy Biopsy Specimen Birds Blood Blood Vessels Blood specimen Body Fluids Body Weight Body Weight decreased Boston Boxing Breeding Bronchi Bronchoalveolar Lavage Bronchoscopes Budgets Buprenex Buprenorphine Burn injury Businesses Calendar Capsid Cardiac Caring Categories Catheters Cause of Death Cells Cellular Immunity Cellular Immunology Certification Cervical Cervix Uteri Cessation of life Chairperson Childhood Clinical Clinical Research Clinical Trials Collaborations Collection Colorectal Commit Committee Members Communication Complement component C1s Confidential Information Consult Consultations Country Culture Media DNA DNA Vaccines DNA vaccine-elicited immunity Data Development Devices Diarrhea Diet Direct Costs Disclosure Disease Dissection Distress Doctor of Philosophy Dorsal Dose Drug Formulations Duct (organ) structure Duodenum Educational process of instructing Effectiveness Electrodes Electronic Mail Electronics Electroporation Employee Endoscopes Endoscopic Biopsy Engineering Epidemic Equipment Euthanasia Event Excision Exercise Exhibits Experimental Water Deprivation Face Facilities and Administrative Costs Faculty Failure Fasting Fellowship Femoral vein Flow Cytometry Flushing Food Forcep Formalin Foundations Frequencies Fringe Benefit Funding Funding Agency Genital system Genotype Genus Mycobacterium Goals Gold Government Grant Guidelines HIV HIV Antigens HIV Infections HIV vaccine HIV-1 HIV-1 vaccine HIV/SIV vaccine Hand Head Health Insurance Health Priorities Hemorrhage Hemostatic function Heterosexuals Histopathology Home environment Hour Housing Human Human Resources Hybridomas IACUC Ice Image Immune Immune response Immune system Immunity Immunization Immunology Immunology procedure Impairment In Vitro Income Individual Infant Infection Injection of therapeutic agent Injury Inpatients Institutes Institution Instruction Intraperitoneal Injections Investments Irrigation Israel Japan Ketamine Ketamine Hydrochloride Knock-out Laboratories Laboratory Animals Language Laryngoscopes Larynx Lateral Laws Lead Left Letters Lidocaine Life Life Cycle Stages Light Liquid substance Listeria Listeria monocytogenes Literature Location Lung Lymphocyte Macaca mulatta Magnetic Resonance Imaging Mails Maintenance Manuals Marketing Mediation Medical Medical center Medicine Methods Microbiology Minor Modeling Modification Molecular Molecular Biology Molecular Conformation Monitor Monkeys Mucosal Immune Responses Mucosal Immunity Mucous Membrane Mus Muscle NIH Vaccine Research Center Names National Institute of Allergy and Infectious Disease Nature Needles Neurologic ORALIT Operative Surgical Procedures Opportunistic Infections Oral Oral mucous membrane structure Organ Outpatients Ovum Pain Paralysed Pathogenesis Patient Care Pelvis Pennsylvania Peripheral Personal Satisfaction Persons Pharmaceutical Preparations Phase I Clinical Trials Phenotype Philadelphia Physiologic pulse Pilot Projects Plasma Plastics Poison Policies Porifera Positioning Attribute Postdoctoral Fellow Postoperative Period Povidone-Iodine Poxviridae Preparation Primates Principal Investigator Printing Procedures Process Production Progress Reports Proteins Protocols documentation Public Health Quarantine Questionnaires Radioisotopes Reading Reagent Recombinant DNA Recombinant Proteins Recombinants Regulation Regulatory Affairs Reporting Research Research Personnel Research Subjects Research Support Response Elements Riots Risk Assessment Rodent Role Route SIV Safety Saline Sampling Schedule Schools Science Scientist Serotyping Services Shock Signal Transduction Site Skin Societies Son Source Specialist Specimen Speculums Sterility Stimulus Stomach Structure of pyloric ostium of stomach Sum Supervision Surgical incisions Syringes Systems Biology T-Lymphocyte Techniques Technology Telazol Telefacsimile Telephone Testing Time Tissue Harvesting Tissue and Organ Harvesting Tissues Toxin Trachea Training Tranquilizing Agents Transgenic Mice Transgenic Organisms Trauma Travel Treatment Protocols Tube U-Series Cooperative Agreements United States National Institutes of Health Universities Update Urine Vaccinated Vaccination Vaccines Vagina Variant Veins Venipunctures Veterinarians Vicryl Viral Viral Pathogenesis Viral Vector Virus Wages Walkers Walking Weight Wit Woman Work Writing absorption abstracting animal care authority base behavior observation chemical carcinogen chiron vaccine clinical efficacy conformer cost design environmental change experience expiration feeding flexibility gastrointestinal human subject immunogenic immunogenicity implantation improved in vivo inhibitor/antagonist instrument interest intravenous injection irradiation jejunum lymph nodes medical schools meetings microbicide microorganism mucosal site mucosal vaccination mucosal vaccine nanoparticle neutralizing antibody nonhuman primate novel novel strategies pandemic disease pathogen pediatric AIDS pediatric human immunodeficiency virus peer poxvirus vectors pre-clinical preclinical evaluation preclinical study professor programs protective efficacy public health relevance rectal research clinical testing research study response restraint skills symposium text searching tissue culture transmission process tumor uptake vaccine candidate vaccine delivery vaccinology vector vector vaccine vector-based vaccine viral RNA vocal cord web site

项目摘要

. Project Summary/Abstract AIDS continues to be an expanding pandemic. The successful development of a safe and effective HIV vaccine is a global health priority that has been hampered by our current inability to deliver HIV antigens efficiently to the immune system to prime predictable, high frequency, and durable immune responses in humans. To approach this problem, we propose a unique prime-boost vaccine strategy that pairs two live mucosal vectors, Listeria monocytogenes (Listeria, Lm) and adenovirus (Ad), each of which has been tested in clinical trials in humans, and both have shown the ability in small animal models and NHP to elicit strong cellular immunity. The proposal is provoked by our recent observations that mucosal administration of attenuated Listeria followed by a boost by replication-incompetent Ad5 elicited potent peripheral and mucosal T cell responses, and by the development of new Ad variants that circumvent anti-Ad5 immunity. Because most HIV infections result from heterosexual transmission to women, and because the virus targets lymphocytes in the gut and vaginal mucosae for rapid elimination, this project aims by use of these vectors to strengthen immunity and protection at these important mucosal sites. The laboratories of Drs. Dan Barouch at Beth Isreal Deaconess Medical Center and Fred Frankel at the University of Pennsylvania School of Medicine will collaborate to explore the potential synergy of these two vectors. Dr. Frankel will examine vector interactions in mice, while Dr. Barouch will conduct concurrent pilot studies testing these vectors in the nonhuman primate model.

。项目概要/摘要艾滋病仍然是一种不断扩大的流行病。成功开发了一个安全有效的艾滋病毒疫苗是全球健康的优先事项，但我们的努力阻碍了这一点目前无法将 HIV 抗原有效地传递至免疫系统以启动人类可预测、高频且持久的免疫反应。接近针对这个问题，我们提出了一种独特的初免-加强疫苗策略，将两种活疫苗配对粘膜载体，单核细胞增生李斯特氏菌（Listeria，Lm）和腺病毒（Ad），各自已经在人体临床试验中进行了测试，并且都显示出小动物模型和NHP可引发强大的细胞免疫。该提案是我们最近的观察结果引起了减毒李斯特菌的粘膜给药随后，复制无能的 Ad5 的增强引发了有效的外周和粘膜 T 细胞反应，并通过开发新的 Ad 变体来规避抗Ad5免疫。因为大多数艾滋病毒感染是由异性传播引起的对女性来说，因为该病毒的目标是肠道和阴道粘膜中的淋巴细胞为了快速消除，该项目旨在通过使用这些载体来增强免疫力以及对这些重要粘膜部位的保护。博士的实验室。丹·巴鲁克贝丝伊斯雷尔女执事医疗中心和弗雷德弗兰克尔大学宾夕法尼亚医学院将合作探索潜在的协同作用这两个向量。弗兰克尔博士将研究小鼠体内的载体相互作用，而弗兰克尔博士将研究小鼠体内的载体相互作用。巴鲁奇将同时进行试点研究，在非人类身上测试这些载体灵长类动物模型。