Campylobacter vaccine development:a key to controlling enteric diseases.
Worldwide, Campylobacter jejuni is a major cause of diarrhoea and dysentery, with approximately 400 million cases occurring annually. Control of the disease through public health and antibiotic measures is insufficient, and vaccination offers the most promising solution. Infection produces immunity from disease, suggesting that vaccination may produce similar protection. Epidemiological data suggest that there are conserved antigens among serotypes; immunity against which protects against disease. Therefore a monovalent serotype vaccine seems practical. Several antigens on Campylobacter have been found to be immunogenic and, in some cases, associated with virulence. However, none of these proteins have been produced recombinantly in the proper conformation, nor have they been protective in preclinical models. For this reason, live attenuated or inactivated Campylobacter whole cell (CWC) vaccines may be the best approach. Development of an attenuated strain of Campylobacter has been complicated by the fact that the organism is highly transformable. Rec A mutants of Campylobacter have recently been constructed in an attempt to avoid this trait. Such mutants have been made defective in various virulence properties and are being evaluated for safety in preclinical models. Antex Biologics has made an inactivated CWC vaccine using the Company's patented NST (nutriment signal transduction) technology, whereby the cells are grown using physiologically logical conditions to maximise the expression of antigens associated with in vivo virulence. This vaccine has been shown to be safe, immunogenic, and protective in preclinical models of infection. Inclusion of a mucosal adjuvant in the vaccine increases the immunological response to the antigen. Recent Phase I and Phase II clinical trials, using the CWC vaccine formulated with an adjuvant and orally administered, show that the vaccine is safe and immunogenic in human volunteers. The approach used to develop this inactivated whole cell Campylobacter vaccine is also applicable for the rapid development of new vaccines against a variety of mucosal pathogens.
Walker
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Antex Biologics, 300 Professional Drive, Gaithersburg, MD 20879, USA. rwalker@antexbio.com