CHILDHOOD IMMUNIZATION FOR DENTAL CARIES

该项目的目标是研制一种龋齿疫苗。牙科 感染变种菌可引发和传播龋齿 链球菌。临床前和临床试验已经证明， 当变形链球菌链球菌攻击被修改时，龋患率下降。 用来自变形链球菌的抗原免疫，例如， 葡萄糖转移酶(GTF)，降低定殖率。一次 殖民已经在成年人口中站稳脚跟，通过 免疫接种不太可能；然而，大多数儿童不会成为殖民地。 直到18个月以后。针对早期目标的疫苗配方 儿童免疫是合理的。 在对啮齿动物的初步研究中，我们已经表明GTF 微粒，通过加入到聚(乳酸-共聚)中配制而成 羟基乙酸(PLGA)赋形剂，可诱导粘膜免疫 回应。递送系统配方方法的修改如下 现在提出通过GTF提高免疫诱导效率。我们 将对GTF初步研究中使用的PLGA技术进行扩展 并通过将生物粘合剂掺入到 GTF/PLGA颗粒物。拟议第一阶段研究的目的是： 证明这些新的生物粘附剂GTF/PLGA配方将诱导 强大和持续的免疫反应，总体SBIR的目标 儿童龋齿疫苗的开发计划 免疫接种。 建议的商业应用： 口服疫苗的微囊化具有重要的意义 疫苗技术的进步。口服免疫是一种更方便， 更安全，也许更有效的针头疫苗替代品 送货。许多疫苗制造商将是一个潜在的商业 这项技术的开发/利用市场不仅是为了其 适用于龋齿，也可用于粘膜感染。

The objective of this project is a vaccine for dental caries. Dental caries can be provoked and transmitted by infection with mutans streptococci. Preclinical and clinical trials have demonstrated that caries incidence declines when mutans streptococcal challenge is modified. Immunization with antigens derived from mutans streptococci, e.g., glucosyltransferase (GTF), reduces the rate of colonization. Once colonization has taken hold in an adult population, eradication via immunization is unlikely; however, most children do not become colonized until after 18 months of age. A vaccine formulation which targets early childhood immunization is reasonable. In preliminary studies in rodents, we have shown that a GTF microparticulate, formulated by incorporation into a poly(lactic-co- glycolic) acid (PLGA) excipient, was capable of inducing mucosal immune responses. Modifications in the delivery system formulation methods are now proposed to increase the efficiency of immune induction via GTF. We will expand upon the PLGA technology used in the preliminary GTF studies and increase particle uptake by incorporation of a bioadhesive into the GTF/PLGA particulate. The objective of the proposed Phase I studies is to demonstrate that these novel bioadhesive GTF/PLGA formulations will elicit a strong and sustained immune response, the goal of the overall SBIR program being the development of a dental caries vaccine for childhood immunization. PROPOSED COMMERCIAL APPLICATION: Microencapsulation of vaccines for oral delivery present a significant advancement in vaccine technology. Oral immunization is a more convenient, safer, and perhaps, more efficient replacement of needle-based vaccine delivery. Many vaccine manufacturers would be a potential commercial market for development/utilization of this technology for not only its application to dental caries, but also to mucosal infections.