title: Protection of ruminants by Pasteurella haemolytica A1 capsular polysaccharide vaccines containing muramyl dipeptide analogs.
abstract: The capsular polysaccharide (CP) of Pasteurella haemolytica serotype A1 is a poor immunogen for the prevention of pneumonic pasteurellosis of ruminants. To improve CP immunogenicity, vaccines were prepared with 1.0 mg CP dose-1 with and without the synthetic adjuvant, muramyl dipeptide (MDP; range 0.2-1.0 mg) or a lipophilic derivative, MDP-sn-glyceryl-dipalmitoyl (MDP-GDP; range 0.1-1.0 mg). The optimum effective concentration of adjuvant was first determined in lambs and calves and then the efficacy of CP +0.5 mg MDP and CP +1.0 mg MDP-GDP was compared with that of two commercial vaccines in calves. After immunization with CP, antibody titers in lambs and calves were typical of that seen with polysaccharide immunogens and characterized by an early IgM response followed by later IgG1 and IgG2 responses. CP + MDP or MDP-GDP vaccines induced significantly higher IgM, IgG1, and IgG2 titers. After transtracheal challenge of immunity with P. haemolytica serotype A1, extensive pulmonary consolidation containing P. haemolytica (10(6)-10(8) c.f.u. g-1) was seen in all lambs and calves vaccinated with CP alone and was not significantly different (P < 0.05) from the consolidation and concentrations of organisms in nonvaccinated challenge controls. In lambs, vaccines containing 1.0 mg CP +0.05 mg MDP or MDP-GDP significantly reduced pulmonary consolidation and concentrations of P. haemolytica in lung lesions. In calves, vaccines containing 0.2 mg MDP, 0.5 mg MDP, or 1.0 mg MDP-GDP also significantly reduced pulmonary consolidation and concentrations of P. haemolytica in lung lesions. Vaccines containing CP +0.5 mg MDP and CP +1.0 mg MDP-GDP induced high titer bactericidal antibodies by 7 days and were more efficacious than two commercial vaccines. Potentiation of CP with MDP or MDP-GDP has great promise in furthering the potential of CP as a vaccine immunogen for the prevention of pneumonic pasteurellosis.
authors.affiliation: National Animal Disease Center, Agricultural Research Service, US Department of Agriculture, Ames, IA, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Brogden
authors.forename: B
authors.initials: B
authors.lastname: DeBey
authors.forename: F
authors.initials: F
authors.lastname: Audibert
authors.forename: H
authors.initials: H
authors.lastname: Lehmkuhl
authors.forename: L
authors.initials: L
authors.lastname: Chedid
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D016667:Bacterial Capsules / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D016978:Mannheimia haemolytica / Q000276:immunology*; D010326:Pasteurella Infections / Q000473:pathology / Q000517:prevention & control* / Q000662:veterinary*; D012766:Pasteurellosis, Pneumonic / Q000473:pathology / Q000517:prevention & control*; D012756:Sheep; D012757:Sheep Diseases / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D000119:Acetylmuramyl-Alanyl-Isoglutamine