Lactococcal vaccine for strep throat

描述（由申请人提供）：目前没有针对“链球菌性咽喉炎”的疫苗，该疾病每年在美国折磨约2000万人（主要是婴儿和12岁以下的儿童）。链球菌性咽喉炎占所有临床就诊的10%至30%。不太常见，但更严重的疾病可能是由未经治疗的链球菌咽喉感染引起的。一种疫苗可以预防疼痛的喉咙痛，减少抗生素的使用，减少上学或工作日的损失。 该项目的长期目标是研制一种安全、有效和经济的疫苗，预防A组链球菌（“链球菌咽喉”）感染引起的急性咽炎。第一阶段要完成的近期目标是：1）优化酿脓链球菌M6蛋白保守C-重复区（CRR）在乳酸乳球菌中的表面表达; 2）优化疫苗剂量和时间表，并确定两种重组L.乳酸链球菌将在小鼠中产生对CRR的最大免疫应答; 3）用3种不同血清型的S.化脓和测量保护免受咽部感染。 该项目将在动物身上测试一种独特的疫苗，这种疫苗是由两种基因pip和emm 6c拼接而成的。emm 6c基因编码来自S的部分蛋白质（M6）。化脓性链球菌，“链球菌性咽喉炎”的病原体。针对M6的抗体可预防链球菌咽喉感染。Pip是M6在非致病性细菌L.乳酸。小鼠将用乳球菌的活培养物经鼻接种，所述乳球菌产生由pip-emm 6c编码的剪接蛋白的两种变体之一。将在血液和唾液中测量针对由pip-emm 6c编码的蛋白质的免疫应答。接种疫苗的小鼠将用感染剂量的3种不同血清型的S.化脓将进行咽喉培养以测量病原体的定殖（感染）。该项目的假设是：1）疫苗将在血液和唾液中产生对M6蛋白的免疫应答; 2）这种免疫应答将保护接种动物免受许多不同血清型S.化脓

DESCRIPTION (provided by applicant): There is currently no vaccine for "strep throat", which annually afflicts about 20 million persons in the US (mostly infants and children under 12 years of age). Strep throat accounts for 10 to 30 % of all clinical visits. Less frequent, but more serious diseases can result from untreated strep throat infections. A vaccine would prevent painful sore throats and reduce the use of antibiotics and loss of school or work days. The long-term goal of the project is to develop a safe, effective and economical vaccine against acute pharyngitis caused by group A streptococcal ("strep throat") infections. The immediate, short term goals to be accomplished in phase I are: 1) Optimize surface expression in Lactococcus lactis of the conserved C-repeat region (CRR) of the M6 protein of Streptococcus pyogenes; 2) Optimize vaccine dose and schedule and determine which of two recombinant strains of L. lactis will produce in mice a maximal immune response to CRR; 3) Challenge vaccinated mice with 3 different serotypes of S. pyogenes and measure protection from pharyngeal infection. The project will test in animals a unique vaccine constructed by splicing together two genes, pip and emm6c. The emm6c gene encodes part of a protein (M6) from S. pyogenes, the causative agent of "strep throat". Antibodies directed against M6 prevent strep throat infection. Pip acts as a carder for expression of M6 on the surface of the non-pathogenic bacterium, L. lactis. Mice will be vaccinated nasally with live cultures of Lactococcus that produce one of two variations of the spliced protein encoded by pip-emm6c. The immune responses against the proteins encoded by pip-emm6c will be measured in the blood and saliva. Vaccinated mice will be challenged with an infectious dose of each of 3 different serotypes of S. pyogenes. Throat cultures will be taken to measure colonization (infection) by the pathogen. The hypotheses of this project are: 1) the vaccine will produce an immune response in both the blood and the saliva to the M6 protein; and 2) this immune response will protect the vaccinated animals against infection by many different serotypes of S. pyogenes