Experiments were performed using the standardized murine model of Helicobacter pylori infection to determine the immunogenicity of H. pylori outer membrane vesicles in immune protection. These vesicles, which are naturally shed from the surface of the bacterium, induce a protective response when administered intragastrically to mice in the presence of cholera holotoxin, despite the absence of the urease enzyme and associated Hsp54 chaperonin. Immunoblotting identified a specific serum immunoglobulin G (IgG) response to an 18-kDa outer membrane protein in a significant number of immunized animals. This commonly expressed, immunodominant protein was subsequently identified as lipoprotein 20 (Lpp20). Hybridoma backpacks secreting an IgG1 subclass monoclonal antibody to Lpp20 were generated in H. pylori-infected mice and were found to significantly reduce bacterial numbers, providing evidence that this surface-exposed antigen is a true vaccine candidate and not merely an antigenic marker for successful, protective immunization.Helicobacter pylori, a bacterium which is estimated to infect more than half the world's population, is associated with peptic ulcer disease (4) and the development of gastric cancer (32). Immunization against this bacterium represents a cost-effective strategy to reduce global gastric cancer rates (5) and would also have a major impact on H. pylori-related peptic ulcer disease. H. pylori vaccine candidates identified to date include the urease enzyme (20,40,51,55) and the urease enzyme chaperonin heat shock protein A (21). Mice immunized with purified VacA cytotoxin are also protected from challenge with a Tox ϩ strain of H. pylori (48). A common factor among these three vaccine candidates is their reported association with the outer membrane of H. pylori (1,16,17,27,36,52,57). The potential of catalase as an H. pylori vaccine candidate has also been identified (58). This enzyme, which is found in both the cytosol and the periplasmic space of H. pylori (28), is also thought to be surface exposed (57). More recently, the screening of recombinant H. pylori antigens (30) has identified another five potential H. pylori vaccine candidates. These include Lpp20, a conserved H. pylori lipoprotein that is membrane associated but not surface exposed (38).In our search for candidate H. pylori vaccine antigens, we have focused on the outer membrane of the bacterium. Like many other gram-negative bacteria (reviewed in reference 25), H. pylori and Helicobacter felis shed part of their outer membrane as vesicles when grown under certain conditions (34). These outer membrane vesicles (OMV) are thought to be formed when the outer membrane of the bacterium expands faster than the underlying peptidoglycan layer, resulting in portions of the membrane blebbing off the surface of growing cells (44). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis reveals that the protein and lipopolysaccharide content of these OMV closely resembles that of a Sarkosyl-insoluble outer membrane preparati...

Purpose - This paper looks into the functional food and nutraceutical registration processes in Japan and China. The Japanese have developed the Foods for Specified Health Use (FOSHU) registration process whereas the Chinese have put into place the Health Food (HF) registration process. The aim of this paper is to compare the regulation processes between the two countries in search for answers to three core empirical questions: (1) how have the registration processes developed and changed? (2) What are the similarities and differences between the processes of registration in the two countries investigated? (3) Why are the registration processes similar/different? Method – The study was conducted using secondary sources. The literature surveyed covered academic journals, trade journals, magazine and newspaper articles, market reports, proceedings, books and web pages of relevant regulatory authorities and regulatory consultants. Information from the more recently published sources was used preferentially over older sources. As well as using the most recent sources, information was selected on the basis of which source it was from. Official regulations and SFDA and MHLW websites would contain accurate and up to date information and information from here would be taken as true over other sources of information. Results - The two diagrams of the registration processes respectively in Japan and China clearly show that there are similarities and differences. There are six categories under which these can be found: (1) the scientific evidence required; (2) the application process; (3) the evaluation process; (4) the law and the categories of products; (5) the labels and the types of claims; and finally (6) the cost and the time involved. Conclusions -The data analysis suggests that the process of diffusion of innovation played a role in the development of the regulations. Further it was found that while Japan was at the outset a pioneer innovator in nutraceutical registration processes, there are indications that in more recent years it too imitated other countries. NOVELTY STATEMENT: The assortment of regulatory regimes creates much uncertainty for the firms and the lack of familiarity and poor knowledge of the regulatory situation increases the risk of failure. The research presented in this paper provides highly valuable information to any biotech/pharmaceutical/nutraceutical companies developing their market entry strategy in Japan and China. There are few national and international studies of drug registration application processes but even fewer comparative studies of functional food and neutraceutical registration application processes such as this one and none using a diffusion of innovation perspective.