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Improved Influenza Vaccine Efficacy Through Infection Mimicry

通过感染模拟提高流感疫苗的功效

基本信息

批准号：
10112817
负责人：
Kathryn Kosuda
金额：
$ 99.99万
依托单位：
VAXESS TECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-15 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10112817
关键词：
Address Affinity Age-Months Animal Model Antibodies Antibody Response Antigen Presentation Antigens Benchmarking Biocompatible Materials Body Temperature Bolus Infusion CD8B1 gene Cells Centers for Disease Control and Prevention (U.S.)Cessation of life Clinic Clinical Data Dermis Detection Development Devices Disease Engineering Exposure to Ferrets Fibroins Formulation Generations Goals Gold Histopathology Hospitalization Human Immune Immune response Immune system Immunization Immunize Immunoglobulin G Immunologics Individual Infection Influenza Influenza vaccination Injections Interferon Type II Intramuscular Injections Kinetics Knowledge Leucocytic infiltrate Lung Manufacturer Name Modeling Mucosal Immunity Mucous Membrane Mus Mutation Outcome Patients Perception Phase Phase I Clinical Trials Population Positioning Attribute Proteins Public Health Risk Assessment Rodent ST14 gene Safety Seasons Serum Silk Skin Source Structure of germinal center of lymph node Symptoms System T cell response T-Lymphocyte Technology Time Toxic effect Translations Vaccine Antigen Vaccines Viral Virus Work World Health Organization anti-influenza base burden of illness clinically relevant combat compliance behavior design flu immunogenicity improved in vivo influenza infection influenza virus vaccine influenzavirus intradermal injection lymph nodes manufacturability meetings mimicry mouse model prevent primary outcome protective efficacy response seasonal influenza trafficking universal vaccine vaccine delivery vaccine efficacy vaccine response

项目摘要

Project Summary/Abstract The World Health Organization estimates that influenza viruses cause serious illness in 3 to 5 million people and up to 650,000 deaths globally each year. While seasonal vaccines to prevent influenza infection are available, frequent mutations in the virus require manufacturers to guess which strains will circulate each season and reformulate vaccine on an annual basis. As a result, the public health impact of seasonal vaccines is limited due to challenges with product efficacy (estimated at 36% for the 2017-18 season). This challenge highlights the critical need for improving current influenza vaccines through strategies to both improve humoral responses (onset, magnitude, and breadth) and generate additional responses such as mucosal immunity and CD4/CD8 cellular responses. Our technology focuses on engineering the sustained release of seasonal influenza vaccines to mimic infection kinetics over 1-2 weeks, providing greater breadth of anti-influenza antibodies and inducing T cell responses. This is accomplished through the use of silk fibroin biomaterial in a microneedle array format that can be easily administered to the skin. The design of the microneedles is such that after a brief 5 minute wear time, the silk microneedle tips are released from the patch and are embedded in the dermis. These silk tips have been engineered to both stabilize vaccine antigens at body temperature while slowly releasing this payload over 1-2 weeks. Our central hypotheses include: (1) sustained antigen presentation mimicking natural infection kinetics can enhance influenza vaccine responses, including greater breadth of protection, and (2) microneedle delivery could simplify patient administration while also improving antigen delivery to immune cells in the skin. These hypotheses are supported by our preliminary data with this strategy, demonstrating significant improvements to the humoral and cellular responses elicited by influenza vaccination. As such, we aim to advance our product towards the clinic through further optimization of the composition of our silk microneedles and by demonstrating their immunogenicity, manufacturability, and safety in IND-enabling studies. Successful completion of our objectives will position the technology for a Phase I clinical trial with the ultimate goal of reducing the global burden of influenza.

项目总结/文摘