Vaccination against Salmonella infections in food animals: rationale, theoretical basis and practical application
During the early years of the last three decades, the animal- and public-health problems associated with Salmonella in poultry increased to such an extent to become major political issues, of which the general public become very aware. Salmonella Enteritidis, in particular, became a worldwide problem, arising mainly from poultry (Rodrigue et al ., 1990). In many countries, individual phage types of this serovar replaced S. Typhimurium as the most dominant type in poultry and humans. Control in poultry has become a major issue and immunity, whether acquired or, more speculatively, innate, is seen as one of the possible means of containing the problem. As a result, Commission Regulation (EC) No 1177/2006 (EC, 2006) prescribes the application of vaccination programmes against S. Enteritidis, at least during rearing, for all laying hens providing they did not demonstrate a prevalence of less than 10% (EC, 2006). In the UK cattle industry, clinical salmonellosis in its acute and chronic forms, together with subclinical infection, remains a major economic, welfare and health problem. While the incidence of acute clinical salmonellosis in pigs is less of a problem compared with that of cattle, subclinical Salmonella infections that result in carcass contamination lead to the introduction of the organism into the food-chain (EFSA, 2008). Widespread use of antibiotics has led to the emergence of multiple antibiotic-resistant bacteria, especially S . Typhimurium. These problems have indicated to the industry and government agencies an increasing requirement for effective vaccines to control this important zoonotic infection. This review discusses the reasons for the relatively poor success in immunizing food animals against those non-host-specific Salmonella serovars that usually produce food poisoning, compared with the success obtained with the small number of serovars that more typically produce systemic _etyphoid-like_f diseases in a restricted range of host species. Most of our understanding of immunity to salmonellosis arises from experimental work with typhoid-like diseases, mainly S. Typhimurium infection in mice. Such work may not be entirely relevant to the, often disease-free, colonization by most Salmonella serovars. However, during the last decade our knowledge, especially on the immune response of poultry after exposure to non-host-adapted serovars, has increased considerably. Whereas live, attenuated vaccines against host-specifi c serovars are highly protective, similarly developed vaccine strains have traditionally been less effective in protecting chickens, calves and pigs against intestinal colonization. Newer methods of attenuation are being developed, but their exploitation and success will depend on appropriate attenuation, delivery, their use for the types of infection that have been shown to be amenable to immune control and their effectiveness under fi eld conditions. One of the key questions is to fi nd the balance between an accepted level of attenuation and an unaffected ability to induce protection involving innate as well as adaptive immunity. This will be possible realistically only through the use of molecular genetics to generate precisely defi ned Salmonella mutants. From the point of view of consumer safety there is a school of thought that considers inactivated or subunit vaccines to be the safest. The benefi ts of developing effective killed or subunit vaccines over the use of live vaccines are enormous. Recently, there have been signifi cant advances in the development of adjuvants, for example microspheres or cytokines, which are capable of potent immunostimulation and modulating the immune response in a more controlled and specific manner (Morein et al. , 1996; Schmidt et al. , 2007; Dey and Srivastava, 2011). The exploitation of such technology in conjunction with the ongoing developments in identifying key Salmonella virulence determinants should form the next generation of Salmonella subunit vaccines for the control of this group of pathogens.