Delivery of Powdered Vaccines for Improving Newborn Vaccination

提供粉状疫苗以改善新生儿疫苗接种

基本信息

批准号：
10092941
负责人：
Mei X Wu
金额：
$ 24.73万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10092941
关键词：
Address Adjuvant Adjuvanticity Adverse event Age-Months Agonist Agreement Antibodies Antibody titer measurement Antigen-Presenting Cells Antigens Anxiety Area Back Bacteria Birth Blindness Cells Cellular Phone Cessation of life Code Cyclic GMP Deposition Dermis Development Diffuse Disease Dose Encapsulated Engineering Epidermis Freeze Drying Fright Future Genes Haemophilus influenzae type b Home Human Hyaluronic Acid Hydration status Immune response Immune system Immunity Immunization In Vitro Individual Infant Infection Interferons Intramuscular Lipid A MF59 Maternal antibody Mediating Meningitis Modification Mus Needles Newborn Infant Parents Penetration Polysaccharides Powder dose form Production Series Skin Survivors Technology Testing Time Tissues Vaccination Vaccine Antigen Vaccines adaptive immune response aluminum sulfate base biomaterial compatibility booster vaccine dosage efficacy validation healing improved in vivo influenza virus vaccine inorganic phosphate micropore minimally invasive neonatal infection neonatal mice nervous system disorder new technology porcine model reconstitution seal skin irritation skin vaccination uptake vaccination schedule vaccination strategy vaccine delivery

项目摘要

Abstract Objective of this proposal is to engineer a Powder-Laden, Dissolvable MicroNeedle Array (PLD-MNA) to improve newborn Hib vaccination. Due to the immature immune system, most of the newborn vaccines induce suboptimal immune responses and require multiple boosters to induce a protective immunity. The lengthened vaccination schedule, in conjunction with a rapid decline of maternal antibodies after birth, leaves a few months of a vulnerability period to various infections for every newborn, which is the single major factor for a high rate of vaccine- preventable diseases occurring in newborns. To eliminate or greatly shorten the vulnerable period, we identified a potent adjuvant cGAMP, an agonist of the stimulator of IFN genes (STING) that could robustly bolster adaptive immune responses in neonatal mice. We will combine this potent adjuvant and powder-based epidermic vaccination to vigorously augment Hib vaccine and reduce Hib vaccine dosage from the current 4 to 2 doses in this proposal. We will first fabricate PLD-MNA encapsulated with Hib conjugated PRP-T vaccine and cGAMP and characterize its loading capacity and delivery efficiency in both newborn mice and piglets. We will also minimize skin irritation, if there is any, in a piglet model and optimize the dosage of immunization in newborn mice. Aim 2 will validate whether prime at birth and boost 10 days later with PLD-MNA packaged with PRP-T/cGAMP can induce a comparable or superior immune response than four alum/intramuscular immunizations of PRP-T vaccine in the presence of maternal antibodies. This needle-free, potentially home-use vaccination, if successful, would represent a paradigm-shifting technology to augment many vaccines for newborns and infants, because most of current infant vaccines are made in a form of powder and can be directly loaded into the PLD-MNAs and applied to newborns.

抽象的该提议的目的是设计一个富含粉末的，可溶解的微针阵列（PLD-MNA）改善新生儿HIB疫苗接种。由于未成熟的免疫系统，大多数新生儿疫苗会诱导次优免疫反应，并需要多个助推器诱导保护性免疫。加长的疫苗接种时间表，并迅速结合出生后母体抗体的下降，脆弱时期几个月每个新生儿的各种感染，这是高疫苗发生率的单一主要因素可预防的疾病发生在新生儿中。消除或大大缩短弱势群体时期，我们确定了一个有效的辅助CGAMP，这是IFN基因刺激器的激动剂（sting）可以坚固地增强新生儿小鼠的适应性免疫反应。我们将结合这种有效的辅助和基于粉末的表皮疫苗接种以剧烈增强在该提案中，HIB疫苗并将Hib疫苗剂量从当前的4剂量降低至2剂。我们将首先制造用HIB共轭PRP-T疫苗和CGAMP封装的PLD-MNA，并且表征其在新生小鼠和小猪中的负载能力和递送效率。我们还将在小猪模型中最大程度地减少皮肤刺激，如果有的话，并优化了新生小鼠的免疫。 AIM 2将验证10天后出生时的素数和提升使用PLD-MNA用PRP-T/CGAMP包装可以诱导可比或优质免疫在存在的情况下，PRP-T疫苗的四个明矾/肌内免疫接种的反应母体抗体。这种无针，潜在的家庭使用疫苗接种（如果成功）将代表一种范式转移技术，以增加许多新生儿和婴儿的疫苗，因为当前大多数婴儿疫苗都是以粉末形式制成的，可以直接加载到PLD-MNA中并应用于新生儿。