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EP-2268308-B2 - VACCINE FOR PROTECTION AGAINST LAWSONIA INTRACELLULARS

EP2268308B2EP 2268308 B2EP2268308 B2EP 2268308B2EP-2268308-B2

Inventors

  • JACOBS, ANTONIUS, ARNOLDUS, CHRISTIAAN
  • VERMEIJ, PAUL
  • SEGERS, RUUD, PHILIP, ANTOON, MARIA
  • SCHRIER, CARLA, CHRISTINA

Dates

Publication Date
20260506
Application Date
20090416

Claims (3)

  1. A non-live carbohydrate containing composition, the carbohydrate being also found in live Lawsonia intracellularis cells in association with the outer cell membrane of these cells, for use as a vaccine for the protection against an infection with Lawsonia intracellularis, by systemic administration of the vaccine, wherein the carbohydrate containing composition is material resulting from the killing of Lawsonia intracellularis bacteria and wherein the carbohydrate containing composition contains whole cells of killed Lawsonia intracellularis bacteria, wherein the vaccine further comprises antigens of Mycoplasma hyopneumoniae and Porcine circo virus.
  2. A non-live carbohydrate containing composition for use according to claim 1, characterised in that the vaccine comprises an oil in water adjuvant containing oil droplets of sub-micrometer size.
  3. A non-live carbohydrate containing composition for use according to claim 2, characterised in that the adjuvant comprises droplets of biodegradable oil and droplets of mineral oil, the droplets of biodegradable oil having an average size that differs from the average size of the droplets of mineral oil.

Description

The present invention pertains to a vaccine for protection against an infection with Lawsonia intracellularis, a vaccine in this sense being a composition that at least provides a decrease in a negative influence of the infection with Lawsonia intracellularis, such negative influence being e.g. tissue damage and/or clincal signs such as decreased weight gain, diarrhea, etc. Proliferative enteropathy (also called enteritis or ileitis) in many animals, in particular pigs, presents a clinical sign and pathological syndrome with mucosal hyperplasia of immature crypt epithelial cells, primarily in the terminal ileum. Other sites of the intestines that can be affected include the jejunum, caecum and colon. Weanling and young adult pigs are principally affected with typical clinical manifestation of rapid weight loss and dehydration. Natural clinical disease in pigs occurs worldwide. The disease is consistently associated with the presence of intracellular curved bacteria, presently known as Lawsonia intracellularis. In general, oral vaccination against Lawsonia intracellularis has shown to be an economically efficient measure to control Ileitis and to allow a better exploitation of the genetic growth potential of the pig (Porcine Proliferative Enteropathy Technical manual 3.0, July 2006; available from Boehringer Ingelheim). Furthermore, oral rather than parenteral vaccination will reduce the transmission of blood-borne infections such as PRRS via multi-use needles and the reduction of injection site reactions and needles retained in carcasses. It will reduce animal and human stresses, time, labour costs and effort compared to individual vaccination (McOrist: "Ileitis - One Pathogen, Several Diseases" at the IPVS Ileitis Symposium in Hamburg, June 28th, 2004). It is generally understood that the advantage of an attenuated live vaccine approach is that the efficacy of immunity is usually relatively good, as the host's immune system is exposed to all the antigenic properties of the organism in a more "natural" manner. Specifically for intracellular bacterial agents such as Lawsonia intracellularis, the live attenuated vaccine approach is believed to offer the best available protection for vaccinated animals, due to a full and appropriate T cell based immune response. This is in contrast with the variable to poor immunity associated with subunit or killed vaccine types for intracellular bacteria. This is also specifically true for obligate intracellular bacteria such as Lawsonia intracellularis or the Chlamydia sp, which cause pathogenic infections within the mucosa. Studies indicate that whole live attenuated forms of the intracellular bacteria in question are best delivered to the target mucosa, that they are required as whole live bacterial forms to produce a fully protective immune response in the target mucosa but also that they are immunologically superior compared to use of partial bacterial components. It has become a general understanding that a vaccine against Lawsonia intracellularis needs to be administered orally (see i.a. Technical Manual 3.0 as referred to here-above). This is based on the fact that the basis of the body's resistance to Ileitis is the local immunity in the intestine, which is the product of cell-mediated immunity and local defense via antibodies, especially IgA. According to current knowledge, serum antibodies (IgG) do not give any protection simply because they do not reach the gut lumen. It has been demonstrated in studies that oral vaccination produces cell-mediated immunity as well as local production of IgA in the intestine (Murtaugh, in Agrar- und Veterinar-Akademie, Nutztierpraxis Aktuell, Ausgabe 9, Juni 2004; and Hyland et al. in Veterinary Immunology and Immunopathology 102 (2004) 329-338). In contrast, intramuscular administration did not lead to protection. Moreover, next to the general understanding that a successful vaccine against intracellular bacteria has to induce cell-mediated immunity as well as the production of local antibodies, the skilled practitioner knows that only a very low percentage of orally ingested antigens are actually absorbed by the enterocytes, and that the incorporation of Lawsonia intracellularis into the cell is an active process initiated by the bacterium. Accordingly an inactivated vaccine would provide the intestine with insufficient immunogenic antigen (Haesebrouck et al. in Veterinary Microbiology 100 (2004) 255-268). This is why it is believed that only attenuated live vaccines induce sufficient cell-mediated protection in the intestinal cells (see Technical Manual 3.0 as referred to here-above). At present there is only one vaccine on the market to protect against Lawsonia intracellularis, viz. Enterisol ® Ileitis marketed by Boehringer Ingelheim. This vaccine is a live vaccine for oral administration indeed. It is an object of the present invention to provide an alternative vaccine to protect against an infection with Lawsonia intracellu