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A Novel Multi-Antigen Virally Vectored Vaccine against Mycobacterium avium Subspecies paratuberculosis.
Bull TJ, Gilbert SC, Sridhar S, Linedale R, Dierkes N, Sidi-Boumedine K, Hermon-Taylor J
PLoS ONE 2007 2(11):e1229

Selected by | Niyaz Ahmed
Evaluated 6 Dec 2007

Relevant Sections
IMMUNOLOGY > Autoimmunity | Immunity to infections
MICROBIOLOGY > Cellular microbiology & pathogenesis | Medical microbiology
PHARMACOLOGY & DRUG DISCOVERY > Antimicrobial agents | Gastrointestinal & renal pharmacology
PHYSIOLOGY > Gastrointestinal physiology

F1000 Factor: 9.0
Recommendation: Exceptional paper
Tags: Technical Advance, New Finding

Comments:

This novel chimeric vaccine by Bull et al. marks one of the first efforts to tackle the infectious cause of Crohn's disease, the most painful suffering that mankind has ever experienced in the absence of any promised cure, except may be the resection of intestines. Against this background there is a real need to progress this new therapeutic vaccine to GMP manufacture and approved clinical trials in people infected with the causative pathogens, Mycobacterium avium subsp. paratuberculosis (MAP). A range of remedial measures are required for the arrest and reversal of the problems of Crohn's disease in humans and its homologous form, the Johne's disease in cattle. A diagnose and cull policy applied to farm animals will not provide a long term solution. What is urgently needed is a range of modern vaccines targeted at the reduction and then minimization of the burden of infection and continuing source of MAP, from animals and humans. The two secreted and two microbial cell surface MAP antigens expressed by the vaccine carrier viruses do not have homologues in the human genome. There is little evidence that the principal long term outcomes for individuals with Crohn’s disease, such as dependency on drugs with a high side effect profile and the need for major surgery, have improved significantly in 35 years. MAP infection and Johne’s disease in domestic animals and wildlife is fast becoming a global problem. Known to be prevalent in Europe and North America throughout the twentieth century, MAP infection and disease in animals is now rising in former low incidence areas like India, Korea, China and Japan. With it arrive the signs of a rising incidence of chronic inflammation of the intestine of the Crohn’s disease type in people in those countries. The MAP issue is complex. The organisms are very slow growing and can be difficult or impossible to establish in culture. Diagnosis of infection in animals particularly in the early stages is unreliable. Infected animals can excrete huge numbers of these pathogens into the environment where their survival and persistence particularly within protists is open ended. Environmental cycling involves trafficking of MAP infection through wildlife such as rabbits and reinfection of domestic animals. It occurs through deposition of extracted slurry from water treatment plants back onto farmland. There is also a potential for the dispersal of these pathogens in aerosols and for the cycling of human strains of MAP within human populations. Passage of these robust versatile organisms within such cycles extends the opportunity for their evolution and enhancement of pathogenicity. Humans are exposed to MAP from sources of environmental contamination and in milk supplies. Influenced by the phenotype and strain of the organism the outcome of such exposure may be the acquisition of some natural resistance. In other cases it may lead to persistent colonisation which, in the presence of particular microbial virulence and the inherited or acquired susceptibility of the host, may eventually lead to the emergence of chronic inflammation of the intestine with features closely resembling that of paucimicrobial Johne’s disease in animals. The reliable scientific evidence for the involvement of strains of MAP in the causation of Crohn’s disease has become very strong. Common conditions such as Irritable Bowel Syndrome, as well as others, are on the list of additional disease candidates. The MAP problem presents as a silent, slowly evolving epidemic whose progression with all its agricultural and human costs, will continue until the true nature of the threat is at last recognised.


Competing interests: Niyaz Ahmed edited and recommended this paper for publication in PLoSONE.

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