CHILDHOOD IMMUNIZATION FOR DENTAL CARIES

该项目的目标是研制龋齿疫苗。牙科 龋齿可以通过感染变形菌引起和传播 链球菌。临床前和临床试验已经证明， 当改变变链菌攻击时，龋齿发病率下降。 用衍生自变形链球菌的抗原免疫，例如， 葡萄糖基转移酶（GTF），降低定殖率。一旦 殖民化已经在成年人口中站稳脚跟，通过 免疫是不可能的;然而，大多数儿童不会成为殖民地， 直到18个月大之后。一种针对早期的疫苗制剂 儿童免疫是合理的。 在啮齿类动物的初步研究中，我们已经表明， 微粒，通过掺入聚（乳酸-共- 羟基乙酸（PLGA）赋形剂，能够诱导粘膜免疫 应答递送系统配制方法的修改是 现在提出通过GTF增加免疫诱导的效率。我们 将扩大在初步GTF研究中使用的PLGA技术 并通过将生物粘附剂结合到 GTF/PLGA颗粒。拟议第I期研究的目的是 证明这些新型生物粘附性GTF/PLGA制剂将引起 一个强大而持续的免疫反应，整体SBIR的目标 儿童龋齿疫苗开发计划 次免疫 拟定商业应用： 用于口服递送的疫苗的微囊化呈现显著的 疫苗技术的进步。口服免疫是一种更方便， 更安全，也许更有效地替代针式疫苗 交付.许多疫苗制造商将是一个潜在的商业 开发/利用这项技术的市场不仅是其 适用于龋齿，也适用于粘膜感染。

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.