SVIBOR - Project code: 3-03-307

MINISTRY OF SCIENCE AND TECHNOLOGY

Strossmayerov trg 4, HR - 10000 ZAGREB
tel.: +385 1 459 44 44, fax: +385 1 459 44 69
E-mail: ured@znanost.hr

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Project code: 3-03-307


Colibacillosis: immunopathology and immunoprophylaxis of diarrheal diseases in pigs


Main researcher: VALPOTIĆ, IVICA (66266)


Assistants
Type of research: applied
Duration from: 01/01/91. to 12/31/95.
Papers on project (total): 64
Papers on project quoted in Current Contents: 16
Institution name: Veterinarski fakultet, Zagreb (53)
Department/Institute: Department of Biology Veterinary Faculty University of Zagreb
Address: Heinzelova 55
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (01)2390-144
Fax: 385 (01)214-697
E-mail: 161.53.93.3.valpotic
Summary: Postweaning colibacillosis is an economically significant disease in swine for which no effective vaccine is available. Porcine F4 (K88)+ enterotoxigenic Escherichia coli (ETEC) strains are recognized as a major cause of diarrheal disease in suckling and weaned pigs. It is assumed that the harmful effects of ETEC are due entirely to enterotoxins and that nontoxigenic (non-ETEC) fimbriated strains of E. coli should be effective and safe oral vaccines. Much of the work of caracterizing porcine intestinal mucosal immune system and developing oral vaccines has focused on the humoral immunity against F4 (K88)+ enterotoxigenic Escherichia coli (ETEC) strains. The current research will investigate the harmful effects and immunogenicity of genetically-engineered non-toxigenic E. coli strains containing wild-type or recombinant plasmids encoding F4 antigen to establish the role of the fimbrial antigen in 1) causing diarrhea and mucosal damage, 2) inducing an inflammatory response of gut-associated lymphoid tissue (GALT), and 3) stimulating the protective immune response at the mucosal surfaces mediated by the cellular elements of GALT. Non-ETEC strain 2407 expressing F4ac fimbrial antigen induced only a mild mucosal damage and was able to invoke moderate leukocyte infiltration in jejunum/ileum. Among T lymphocytes an increase of CD8a+, CD4a+, or SWC1a+/CD8a+ cells in lamina propria (LP), Peyer's patches (PP) and mesenteric lymph node (MLN), respectively, was observed. Both non-ETEC strains (1466 and 2407) activated lymphocytes from PP and MLN to respond better to common mitogens, F4ac antigen or immonologic response modifiers (IRMs). The results indicate that F4ac+ non-ETEC strain 2407 seems to be the best source of protective antigen in developing of safe and effective live oral vaccine against postweaning colibacillosis. However, before any firm conclusions (and field trial), it is necessary to study the vaccinal antigen using 1) F4 receptor-positive (susceptible) and -negative (resistant) pigs, and 2) IRMs (peptidoglycan monomer and Baypamun) applied in vivo along with non-ETEC strain 2407.

Keywords: postweaning colibacillocis, ETEC/non-ETEC, cellular immunity, intestinal mucosa, vaccine.

Research goals: The basic hypothesis of the project assumes that F4 antigen of enterotoxigenic E. coli (ETEC) strain, and also of non-ETEC strains, could induce besides well known local humoral immune response (secretory IgA), less studied cellular immune response of porcine gut-associated lymphoid tissues (GALT). The later response should be exhibited through enhanced infiltration and reactivity (proliferation) of lymphoid cells in small mesenteric lymph nodes (MLN) of weaned pigs. From this hypothesis three main questions arose: (1) whether or not F4+ non-ETEC strains (authentic or recombinant) are able to invoke an equally strong cellular immune response in the GALT as F4+ ETEC strain does, without causing damage in the small intestinal mucosa of experimentally infected pigs, (2) is it possible to enhance nonspecifically the intestinal protective immunity, that was established (after ETEC/non-ETEC inoculation), by means of immune response modifiers (IRM), and (3) would it be practically feasible that orally applied allogeneic immunoglobulins (Ig) or fimbrial vaccine can protect pigs from naturally or artificially induced diarrheal disease due to E. coli infections. These questions should be answered through the following objectives of the research: - determine frequency and significance of intestinal F4 receptor for adhesion of F4+ ETEC strains in pigs and develop the practical test for identification of genetically resistant (receptor-negative) swine; - test the protective ability of fimbrial vaccine Colimix in specific, and allogeneic Ig in nonspecific immunoprophylaxes of diarrheal disease caused by F4+ ETEC strains in genetically susceptible and resistant pigs; - determine the quantitative proportions and demonstrate in situ distribution of T lymphocyte subsets (SWC1+, CD2+, CD4+, CD8+ cells) in LP, PP and MLN of pigs inoculated with F4+ ETEC or non-ETEC strains; - assess the functional properties of T and B lymphocytes from the GALT in in vitro stimulation tests using common mitogens, F4 antigen, or IRM after in vivo activation with F4 fimbrial and/or enterotoxin antigens; - determine the extent and intensity of mucosal lesions in the small intestine (at microscopic and ultrastructural levels) of experimentally infected pigs. The results obtained on the basis of these objectives would contribute to our understanding of a role and effectiveness of local (intestinal) cellular immune mechanisms in the GALT against bacterial infection, and enable development of a safe (without toxins) and effective (with F4 immunogen) live oral vaccine against colibacillosis caused by F4+ ETEC strains in postweaning pigs.

COOPERATION - PROJECTS


  1. Name of project: 3-03-301 Trihineloza: Imunologija i imunopatologija zoonoze
    Name of institution: Zavod za parazitologiju i invazijske bolesti, Veterinarski fakultet, Sveučilišta u Zagrebu
    City: 10000 - Zagreb, Croatia

  2. Name of project: 3-03-315 Kontrola dominantnih bakterijskih infekcija svinja
    Name of institution: Veterinarski institut, Zagreb
    City: 10000 - Zagreb, Croatia

  3. Name of project: 3-03-299 Utjecaj paragenetskih faktora na patologiju u svinja
    Name of institution: Zavod za patologiju i patološku morfologiju, Veterinarski fakultet, Sveučilišta u Zagrebu
    City: 10000 - Zagreb, Croatia

  4. Name of project: 3-03-340 Mikroklima i etologija u svinjogojskoj proizvodnji
    Name of institution: Zavod za zoohigijenu, Veterinarski fakultet, Sveučilišta u Zagrebu
    City: 10000 - Zagreb, Croatia

  5. Name of project: FG-CRO(YU) 933 Monitoring of swine pathology II
    Name of institution: Zavod za patologiju i patološku morfologiju, Veterinarski fakultet, Sveučilišta u Zagrebu
    City: 10000 - Zagreb, Croatia

  6. Name of project: 1-08-303 Tumori i metastaze : Biologija i liječenje
    Name of institution: Zavod za animalnu fiziologiju Prirodoslovno-matematičkog fakulteta, Sveučilišta u Zagrebu
    City: 10000 - Zagreb, Croatia

COOPERATION - INSTITUTIONS


  1. Name of institution: National Animal Disease Center, Ames, Iowa, SAD, US Department of Agriculture, Agricultural Research Service
    Type of institution: State institute
    Type of cooperation: Joint project
    City: 50010 IA - Ames, SAD

  2. Name of institution: Veterinary Institute of Hungarian Academy of Sciences, Budimpešta, Mađarska
    Type of institution: State institute
    Type of cooperation: Occasional exchange of information
    City: HA-1581 - Budapest, Mađarska

  3. Name of institution: University of Bristol, Veterinary Faculty
    Type of institution: University/Faculty
    Type of cooperation: Joint project
    City: Bristol, Velika Britanija
Other information about the project.
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