SBIR Phase I: Incorporation of a new adjuvant system to produce a thermally stable, orally administered Diphteria-Tetanus-Pertussis vaccine

该SBIR第一阶段项目将测试将新型疫苗技术结合到白喉、破伤风和无细胞百日咳（DTaP）疫苗中以生产热稳定的口服制剂的可行性。疫苗是全球公共卫生领域的最佳投资之一，据估计，每年可挽救200万至300万人的生命，保护1亿多人免受疾病和残疾之害。该项目提出使用一种新型疫苗技术平台，该平台靶向肠道中的免疫细胞，产生广泛的免疫反应，并在室温下保持稳定性。这项技术有可能最大限度地减少对冷链和训练有素的医疗专业人员接种疫苗的依赖，因为冷链和专业人员接种疫苗是实现疫苗全面覆盖的障碍。此外，它有可能增加成人对疫苗加强剂的吸收，方便自我管理，减少焦虑，无需针头。最后，口服DTaP疫苗的成功配制将为口服其他抗原打开大门。这项技术可以显著改善国民健康，这是NSF的使命之一。此外，将疫苗转换为热稳定的口服形式是非常具有成本效益的，并将减轻冷链和专业人员接种疫苗的负担和成本。SBIR第一阶段项目将测试一种新的递送技术在DTaP疫苗中的应用。高度创新的递送平台包括一种新型佐剂，一种C型凝集素（CTL）受体配体与氢氧化铝，靶向粘膜免疫细胞，以增强广泛的免疫反应，以及疫苗的微胶囊化，以抵抗胃的强酸性环境。这项技术可以被纳入现有的或新的疫苗，提高稳定性，并允许口服。该项目的第一个目标包括将CTL受体配体掺入DTaP疫苗，并将肠溶微胶囊化颗粒以保护疫苗免受低pH的影响。将进行广泛的测试和实验以获得最终口服疫苗的最佳配方。第二个目标是在小鼠中测试和比较新配制的疫苗与市售DTaP疫苗的效力。最终目标是测试和比较两种疫苗在高温下的稳定性。所有目标的成功完成将为该技术的商业可行性提供一个很好的基础。这项技术有可能被纳入任何疫苗，可以受益于一个热稳定和口服交付平台。这一奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的知识价值和更广泛的影响审查标准的支持。

This SBIR Phase I project will test the feasibility of incorporating a novel vaccine technology to diphtheria, tetanus, and acellular pertussis (DTaP) vaccine to produce a thermostable and orally administered formulation. Vaccines are one of the best investments in global public health and are estimated to save 2-3 million lives per year and protect more than 100 million lives from illness and disability. This project proposes to use a novel vaccine technology platform that targets immune cells in the intestine, enducing a broad immune response, and retains stability at room temperature. This technology has the potential to minimize dependence on the cold-chain and trained medical professionals to administer the vaccine, which are barriers to full vaccine coverage. Additionally, it has potential to increase uptake of vaccine booster doses for adults, with convenience of self-administration and reduced anxiety with no needles. Finally, successful formulation of an oral DTaP vaccine would open the doors to other antigens to be delivered orally. This technology can significantly improve national health, which is one of the missions of NSF. Additionally, switching vaccines to thermostable, oral delivery form is very cost-effective and will alleviate the burden and cost of cold-chain and professional to administer the vaccines. This SBIR Phase I project will test the application of a novel delivery technology to the DTaP vaccine. The highly innovative delivery platform consists of a novel adjuvant, a C-type lectin (CTL) receptor ligand with aluminum hydroxide that targets mucosal immune cells for a strong synergistic boosting of broad immune response, and microencapsulation of the vaccine to resist the strong acidic environment of the stomach. This technology can be incorporated into existing or new vaccines enhancing stability and allowing oral delivery. The first goal of this project includes incorporation of CTL receptor ligand to the DTaP vaccine and applying enteric microencapsulation to the particles to protect the vaccine from low pH. Extensive testing and experiments will be conducted to obtain the optimal formulation of the final oral vaccine. The second goal will be to test and compare the potency of the newly formulated vaccine with a commercially available DTaP vaccine in mice. The final goal will be to test and compare the stability of both vaccines at high temperatures. Successful completion of all objectives will provide a great base for commercial feasibility of the technology. This technology has the potential to be incorporated on any vaccine that can benefit from a thermostable and orally delivery platform.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.