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.

抽象的该提案的目的是设计一种充满粉末的可溶解微针阵列 (PLD-MNA) 改善新生儿 Hib 疫苗接种。由于免疫系统不成熟，大多数新生儿疫苗会诱导次优的免疫反应，需要多次加强免疫诱导保护性免疫力。延长疫苗接种计划，同时加快疫苗接种速度出生后母体抗体下降，留下几个月的脆弱期每个新生儿都有多种感染，这是疫苗接种率高的一个主要因素新生儿发生的可预防疾病。消除或大大缩短脆弱性在此期间，我们发现了一种有效的佐剂 cGAMP，它是 IFN 基因刺激剂的激动剂（STING）可以强有力地增强新生小鼠的适应性免疫反应。我们将将这种有效的佐剂和粉状表皮疫苗接种相结合，可大力增强本提案中将 Hib 疫苗接种并将 Hib 疫苗剂量从目前的 4 剂减少到 2 剂。我们将首先制造封装有 Hib 结合 PRP-T 疫苗和 cGAMP 的 PLD-MNA，表征其在新生小鼠和仔猪中的装载能力和输送效率。我们还将最大限度地减少仔猪模型中的皮肤刺激（如果有的话），并优化剂量新生小鼠的免疫接种。目标 2 将验证出生时是否处于最佳状态并在 10 天后进行增强与 PRP-T/cGAMP 包装的 PLD-MNA 可以诱导相当或更好的免疫在存在以下物质的情况下，比四次 PRP-T 疫苗明矾/肌内免疫接种的反应要好母体抗体。这种无针、可能家庭使用的疫苗接种如果成功的话，将代表了一种范式转变技术，可以增强新生儿和婴儿的许多疫苗，因为目前的婴儿疫苗大多是粉末状的，可以直接注射。加载到 PLD-MNA 中并应用于新生儿。