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Novel mechanisms of live, bacterial vaccines in protection against salmonella and other food-borne zoonoses

Last updating 1999

Contract nr: FAIR-CT98-4006
Project nr: 4006
Project type: SC
Starting date: 04/01/1999
Duration: 36 months
Total cost: 1,832,075 EUR
EC Contribution: 1,143,602 EUR
Scientific Officer: Isabel MINGUEZ-TUDELA
Research topic: Animal health

Boultry remains one of the most important sources of food-poisoning Salmonella serotypes for man in Europe and many other parts of the world. This has been recognized within the European Union, both by legislation (Directive 92/117) and by networks set up between research groups for information exchange such as COST Action 97. Because of the economic problems inherent in controlling Salmonella infection in poultry by improvements in housing, feed and carcass processing it is likely that biological methods for control will become increasingly important as a component of comprehensive control schemes. Antibiotic usage is undesirable because of the development of resistance and normal flora administration to chicks is able to increase resistance only to the level of the non-immune adult bird. Killed vaccines are ineffective against intestinal infection. Live, attenuated vaccines are therefore likely to become increasingly attractive to the poultry industry and some vaccines containing undefined mutations are already on the market. Live vaccines have been shown experimentally to be an effective means to increase the resistance of chickens to Salmonella infection. However, because of the delay involved in the development of immunity after vaccination, newly-hatched chicks remain highly susceptible to early infection as might arise from hatcheries. The same applies to early-weaned piglets and to very young calves. Experimental observations made within the last decade have shown that oral inoculation of very young chickens with either wild-type Salmonella strains or live, attenuated vaccines result in extensive intestinal colonization which eonfers on the chiek a profound resistance to oral infection with other Salmonella strains inoculated afterwards. The development of resistance is rapid and occurs within 8-16 hours of administration of the first strain. We refer to this effect as colonization-inhibition. We believe the effect is closely related to the growth-suppression that occurs in stationary-phase nutrient broth cultures. The effect means that appropriate live vaccines may be administered orally to young chicks inducing rapid resistance by this microbiological phenomenon and, additionally, stimulating immunity in the normal way. Additional experiments in gnotobiotic pigs have demonstrated a rapid development of non-specific immunity, not related to the microbiological effect, and expressed at the level of the intestine.

The project is intended to increase our understanding of these phenomena both at a theoretical level and as a practical means for inclusion in an immunity regimen as part of a comprehensive means for Salmonella control. We intend to examine the microbiological effect by creating transposon mutants and identifying the genes affected in those mutants which do not show the colonization-inhibition effect. We intend to identify a volatile chemical present in stationary-phase cultures and which might be related to this effect and to examine the role of homo-serine-like compounds in the effect. The role of competition in adhesion to eukaryotic cells between different Salmonella strains will be studied. We intend to examine the non-specific immunity both in chiekens and pigs by analysing, by immunohistoehemistry with monoelonal antibodies which are specific for different lymphocyte and monocyte cell types, the early cellular responses to oral infection with Salmonella strains. Cytokine production will be studied. Lastly, we intend to explore some of the more applied aspects of this effect related to pre-harvest food-safety. These include how effective this effect will be under field conditions using a candidate vaccine strain prepared by attenuating a strain of S. Typhimurium, S. Enteritidis and S. Hadar selected by having a wide spectrum of inhibitory activity. We will additionally test this effect for its ability to prevent morbidity produced by challenge with a highly virulent challenge strain and also to see whether it occurs between strains of other genera sueh as E. Coli and Campylobacter jejuni.

Paul Andrew BARROW
Institute for Animal Health
UK-RG20 7NN Newbury
Tel.: +44 1635 57 72 31
Fax: +44 1635 57 72 37


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    Hoechst Roussel Ver ltd
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  • Gunter STEINBACH
    Bundesinstitut fuer Gesundheitlichen Verbraucherschutz und Veterinaermedizin
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    Veterinary Research Institute
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  • Bela NAGY
    Veterinary Medical Research Institute of the Hungarian Academy of Sciences
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  • Richard DUCATELLE
    University of Ghent
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  • Philippe VELGE
    Institut National de la Recherche Agronomique Centre de Recherche de Tours-Nouzilly
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    Fax: +33 2 47 42 77 79

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