Development of Recombinant SARS VLP Vaccines

重组SARS VLP疫苗的研制

基本信息

批准号：
7184337
负责人：
Gale Smith
金额：
$ 50.96万
依托单位：
NOVAVAX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-02-15 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7184337
关键词：
Acids Adjuvant Adult Affinity Affinity Chromatography Amino Acid Sequence Animal Model Animals Antibody Formation Antigens Applications Grants Baculoviruses Binding Biological Assay Bioreactors Blood Buffers C-terminal Cell Line Cells Chinese Hamster Ovary Cell Chromatography Clinical Clinical Protocols Clinical Research Codon Nucleotides Collaborations Complex Condition Contracts Coronavirus Coronavirus Infections Coronavirus spike protein Coupled Cyclic GMP DNA Sequence Data Development Devices Dihydrofolate Reductase Disease Dose Double-Blind Method Drug Formulations E protein Encapsulated Enzyme-Linked Immunosorbent Assay Evaluation Exclusion Exhibits Extracellular Domain Gagging Gel Chromatography Gene Amplification Generations Genes Genetic screening method Glycoproteins Growth Guanosine Monophosphate Guidelines HIV Harvest Hemagglutinin Histopathology Human Human Influenza A Virus Human Volunteers Infection Insecta Institutes Ion Exchange Isoelectric Focusing Isoenzymes Karyotype Laboratories Laboratory Animals Length Ligands Lipids Macaca fascicularis Mammalian Cell Mass Spectrum Analysis Measures Methods Methotrexate Modeling Mucosal Immunity Mus Oryctolagus cuniculus Oxygen Consumption Peptide Mapping Peptide Sequence Determination Peptides Pharmacology Phase Phase I Clinical Trials Placebo Control Plant Resins Plaque Assay Primates Process Product Container Production Protein Subunits Proteins Qualifying Randomized Rattus Recombinant Proteins Recombinants Relative (related person)Route SARS coronavirus Safety Saliva Sampling Sepharose Serum Severe Acute Respiratory Syndrome Site Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Sprague-Dawley Rats Standards of Weights and Measures Structure of parenchyma of lung Sucrose Syringes System Temperature Testing Tissues Toxicology Ultracentrifugation United States Food and Drug Administration United States National Institutes of Health Vaccines Vaginal Douching Vero Cells Vial device Viral Viral Antigens Viral Proteins Viral load measurement Virus Virus-like particle Week Western Blotting Work aluminum sulfate animal facility body system cell bank cytokine day density diffraction of light env Gene Products evaluation/testing expiration expression vector glycosylation human coronavirus immunogenicity in vivo influenza virus gene influenzavirus light scattering macromolecule microbial nanoparticle neutralizing antibody nonhuman primate novel pre-clinical prevent recombinant virus scale up self assembly size vaccine development vaccine safety vector

项目摘要

DESCRIPTION (provided by applicant): The objective of this grant proposal is to develop and manufacture preclinical and clinical lots of novel recombinant SARS subunit protein vaccines formulated with Novasome adjuvants for evaluation in small animal and primate challenge models to prevent SARS coronavirus infection and disease. This plan will develop three types of SARS vaccine candidates comprised of recombinant SARS coronavirus S, M, and E proteins, which have been codon-optimized, cloned, and expressed in baculovirus-infected insect cells at Novavax, Inc. Vaccine candidates include the following: (1) recombinant multiprotein immunogens displayed on Novasomes, (2) VLPs self-assembled in vivo, and (3) chimeric VLPs comprised of SARS viral proteins and human influenza virus hemagglutinin proteins. Vaccine immunogens, expressed in baculovirus-infected insect cells and/or CHO cells, will be purified by ultracentrifugation and chromatographic methods. Vaccine immunogens will be formulated with adjuvants and will be evaluated initially for mucosal and systemic immunogenicity in mice. Vaccine candidates that elicit SARS neutralizing antibodies in the murine immunogenicity model, as determined by microneutralization assays, will be evaluated further in a novel SARS mouse challenge model in collaboration with Dr. Kanta Subbarao (NIH), who recently developed the model. Preclinical lots of vaccine candidates that elicit neutralizing antibodies and reduce virus titers in the murine challenge model will be tested further in a SARS primate challenge model using cynomolgus monkeys in collaboration with Dr. James Estep (Battelle Institute) in their BSL3 primate facility. Finally, clinical lots of a SARS vaccine candidate that demonstrates the highest SARS neutralizing antibody titer and the greatest virus reduction in the primate challenge model will be manufactured and lot release tested. Toxicology studies of the SARS vaccine candidate will be conducted in rabbits. A clinical protocol for a Phase I clinical study will be prepared, and an IND application will be submitted to CBER/FDA.

描述（由申请人提供）：该赠款提案的目的是开发和制造临床前和临床上的许多新型重组SARS亚基蛋白疫苗，该蛋白质用Novasome佐剂制成，以在小动物和灵长类动物挑战模型中进行评估，以防止SARS冠状病毒感染和疾病。 This plan will develop three types of SARS vaccine candidates comprised of recombinant SARS coronavirus S, M, and E proteins, which have been codon-optimized, cloned, and expressed in baculovirus-infected insect cells at Novavax, Inc. Vaccine candidates include the following: (1) recombinant multiprotein immunogens displayed on Novasomes, (2) VLPs自组装在体内，（3）由SARS病毒蛋白和人流感病毒hemagglutinin蛋白组成的嵌合VLP。在细菌病毒感染的昆虫细胞和/或CHO细胞中表达的疫苗免疫原子将通过超速离心和色谱法纯化。疫苗免疫原子将用佐剂配制，最初将评估小鼠的粘膜和全身免疫原性。通过微中和化测定确定的鼠免疫原性模型中中和抗体的疫苗候选者将在新型的SARS小鼠挑战模型中与Kanta Subbarao博士（NIH）合作进行进一步评估，后者最近开发了该模型。临床前的许多候选疫苗候选者将在Murine挑战模型中使用Cynomolgus Monkeys与James Estep博士（Battelle Institute）在其BSL3灵长类动物设施中合作，在SARS灵长类动物挑战模型中进一步测试中和抗体的疫苗候选者。最后，将制造出最高的SARS疫苗候选者，这些SARS疫苗表现出最高的SARS中和抗体滴度和灵长类动物挑战模型中最大的病毒降低，并测试了批次释放。 SARS疫苗候选者的毒理学研究将在兔子中进行。将准备一项I期临床研究的临床方案，并将IND应用提交给CBER/FDA。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV.

DOI：
10.1016/j.vaccine.2011.06.111
发表时间：
2011-09-02
期刊：
VACCINE
影响因子：
5.5
作者：
Liu, Ye V.;Massare, Michael J.;Barnard, Dale L.;Kort, Thomas;Nathan, Margret;Wang, Lei;Smith, Gale
通讯作者：
Smith, Gale