Campylobacter jejuni outer membrane protein vaccine

描述（由申请人提供）：空肠弯曲杆菌是美国细菌性肠胃炎的主要原因，由于其能够引起食源性和水源性爆发，已被美国国立卫生研究院列为B类生物恐怖制剂。美国每年至少有240万例空肠梭菌病，其发病率超过沙门氏菌和志贺氏菌的总和(5)。空肠梭菌感染也是发展为格林-巴利综合征（GBS）的最常见的前事件，GBS是一种急性运动麻痹，显然是由针对空肠梭菌表面抗原的自身免疫反应引起的。因此，非常需要一种有效的空肠梭菌疫苗，以保护美国人口免受自然发生的空肠梭菌病和潜在的生物恐怖袭击。基于空肠梭菌全细胞制剂的疫苗已被提出，然而，由于GBS发展的不确定性，替代方法是必要的。因此，由高度保守的外膜蛋白（OMPs）组成的疫苗可能最有希望安全地诱导保护性免疫，而不会诱发GBS。

DESCRIPTION (provided by applicant): Campylobacter jejuni is the leading cause of bacterial gastroenteritis in the U.S., and has been classified by the NIH as a Category B Bioterrorism Agent due to its ability to cause food-borne and water-borne outbreaks. There are at least 2.4 million cases of C. jejuni disease in the U.S. annually, with an incidence exceeding that of Salmonella and Shigella combined (5). C. jejuni infection is also the most common antecedent event to the development of Guiilain-Barre Syndrome (GBS), an acute motor paralysis that apparently results from an autoimmune response directed against C. jejuni surface antigens. An effective vaccine against C. jejuni is therefore highly desirable, to protect the U.S. population from both naturally-occurring C. jejuni disease and that arising from potential bioterrorist attacks. Vaccines based on C. jejuni whole-cell preparations have been proposed, however, due to uncertainties concerning the development of GBS, alternative approaches are warranted. A vaccine consisting of highly conserved outer membrane proteins (OMPs) may therefore hold the most promise for safely inducing protective immunity without the potential for inducing GBS. It is well recognized that C. jejuni strains are highly variable, and this will certainly impact on the development of a protein subunit vaccine. A protein appropriate for vaccine inclusion must be conserved in the largest possible proportion of C. jejuni strains, must be immunogenic, and must induce protective immunity against a large number of diverse C. jejuni strains. While analysis of the C. jejuni genome sequence is helpful as a starting point toward understanding its complement of OMPs, only direct identification of OMPs (by proteome analysis) will provide detailed information about the OMPs actually expressed by C. jejuni strains. Hypothesis: Certain C. jejuni outer membrane proteins (OMPs) will be conserved among all C. jejuni strains, will be immunogenic during human infection, and will generate a protective immune response. Specific Aim 1. We will identify the protein constituents of the outer membranes of several C. jejuni strains using proteomics and mass spectrometry. Specific Aim 2. We will determine whether OMPs that are conserved in our initial strains are also found in a large number of C. jejuni strains (fresh clinical isolates and an archival collection of strains from across the U.S.), and will evaluate the immune responses of infected humans to these OMPs. Specific Aim 3. We will determine whether immunization of mice with conserved, purified recombinant OMPs protects against subsequent experimental C. jejuni infection.