title: Intranasal vaccination of calves with Mannheimia haemolytica chimeric protein containing the major surface epitope of outer membrane lipoprotein PlpE, the neutralizing epitope of leukotoxin, and cholera toxin subunit B.
abstract: This study was done to determine if intranasal vaccination of weaned beef calves with a chimeric protein containing the immunodominant surface epitope of Mannheimia haemolytica PlpE (R2) and the neutralizing epitope of leukotoxin (NLKT) covalently linked to truncated cholera toxin (CT) subunit B (CTB) could stimulate secretory and systemic antibodies against M. haemolytica while enhancing resistance of cattle against M. haemolytica intrabronchial challenge. Sixteen weaned beef calves were intranasally vaccinated with CTB-R2-NLKT chimeric (SAC102) or with R2-NLKT-R2-NLKT chimeric (SAC89) protein with or without native CT on days 0 and 14 and were challenged intrabronchially on day 28. In vitro, SAC102 bound the CT receptor molecule, GM(1)-ganglioside. Mean IgA antibodies to M. haemolytica whole cells (WC) and to LKT were high on day 0. A small, yet significant increase (p<0.05) was found in mean nasal antibodies to M. haemolytica WC for the SAC89+CT and SAC102 vaccinates after the second vaccination. SAC102 stimulated significant (p<0.05) mean serum antibody responses to all three antigens by day 28. Following challenge, mean antibodies to WC and LKT significantly increased (p<0.05) for the SAC102, SAC89 and SAC89+CT groups with the mean antibody responses to rPlpE stimulated by SAC102 vaccination being significantly higher (p<0.05) than for the other vaccinated and control groups. On day 1 after challenge, mean clinical score for the control group was significantly higher (p<0.05) than for the SAC102 and SAC89+CT vaccinates, and by day 2 after challenge, clinical score for the control group was significantly higher (p<0.05) than for all three chimeric vaccinated groups. Therefore, intranasal vaccination with CTB-R2-NLKT (SAC102) and R2-NLKT-R2-NLKT (SAC89) chimeric proteins enhanced resistance against intrabronchial challenge with the bacterium as well as stimulating antibody responses to M. haemolytica antigens.
authors: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078-2007, USA.
authors: S
authors: S
authors: Ayalew
authors: D L
authors: DL
authors: Step
authors: M
authors: M
authors: Montelongo
authors: A W
authors: AW
authors: Confer
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D057134:Antibodies, Neutralizing / Q000096:biosynthesis; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000235:genetics; D001483:Base Sequence; D002417:Cattle; D002772:Cholera Toxin / Q000008:administration & dosage*; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D000939:Epitopes / Q000008:administration & dosage / Q000235:genetics; D005098:Exotoxins / Q000008:administration & dosage* / Q000276:immunology*; D005677:G(M1) Ganglioside / Q000378:metabolism; D008074:Lipoproteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D016978:Mannheimia haemolytica / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D012766:Pasteurellosis, Pneumonic / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics
chemical_list: D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D017931:DNA Primers; D004269:DNA, Bacterial; D000939:Epitopes; D005098:Exotoxins; D008074:Lipoproteins; C116100:PlpE protein, Pasteurella haemolytica; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C018579:leukotoxin; D005677:G(M1) Ganglioside; D002772:Cholera Toxin