Protection against Mycoplasma bovis infection in calves following intranasal vaccination with modified-live Mannheimia haemolytica expressing Mycoplasma antigens

Authors: Briggs, Robert; Billing, Sheila; Boatwright, Jr, William; Chriswell, Bradley; Casas, Eduardo; Dassanayake, Rohana; Palmer, Mitchell; REGISTER, KAREN - Retired ARS Employee; Tatum, Fred

Submitted to: Microbial Pathogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/23/2021
Publication Date: 8/29/2021
Citation: Briggs, R.E., Billing, S.R., Boatwright Jr, W.D., Chriswell, B.O., Casas, E., Dassanayake, R.P., Palmer, M.V., Register, K.B., Tatum, F.M. 2021. Protection against Mycoplasma bovis infection in calves following intranasal vaccination with modified-live Mannheimia haemolytica expressing Mycoplasma antigens. Microbial Pathogenesis. 161. Article 105159. https://doi.org/10.1016/j.micpath.2021.105159.
DOI: https://doi.org/10.1016/j.micpath.2021.105159

Interpretive Summary: Mannheimia haemolytica and Mycoplasma bovis are bacteria known to cause pneumonia and other serious disease conditions in cattle. There is a need for new vaccines to control these pathogens because these two bacteria are responsible for substantial economic losses to dairy, cattle, and bison producers. Previously, we have shown by mutating and inactivating the M. haemolytica leukotoxin protein, the bacterium is rendered safe and effective as a vaccine. Extending on this finding, a new M. haemolytica vaccine candidate was made that co-expressed inactive leukotoxin joined to M. bovis proteins. This M. haemolytica vaccine strain was tested in cattle and the vaccinates were protected against many of the disease conditions caused by M. bovis such as middle ear infections, joint infections and lung lesions. Most notably, the amount of M. bovis found in the lungs of vaccinated cattle was dramatically lower than in the unvaccinated controls. These results indicate that this new M. haemolytica strain may serve as a two-way vaccine that protects cattle against both M. bovis and M. haemolytica.

Technical Abstract: Novel live vaccine strains of Mannheimia haemolytica serotypes (St)1 and St6, expressing and secreting inactive yet immunogenic leukotoxin (leukotoxoid) fused to antigenic domains of Mycoplasma bovis Elongation Factor Tu (EFTu) and Heat shock protein (Hsp) 70 were constructed and tested for efficacy in cattle. Control calves were administered an intranasal mixture of M. haemolytica St1 and St6 leukotoxoid mutants ('lktCAV4) while vaccinated calves were administered an intranasal mixture of M. haemolytica St1 and St6 leukotoxoid mutants coupled to the M. bovis antigens (EFTu-Hsp70-'lktCAV4). All M. haemolytica strains were recovered from palatine tonsils up to 34 days post intranasal exposure. On day 35, all calves were exposed to bovine herpes virus-1 and four days later lung challenged with virulent M. bovis. Results showed all cattle produced systemic antibody responses against leukotoxin. The vaccinates also produced systemic antibody responses to M. bovis antigens, and concurrent reductions in temperatures, middle ear infections, joint infections and lung lesions versus the control group. Most notably, dramatically decreased lung loads of M. bovis were detected in the vaccinated cattle. These observations strongly suggest that modified-live M. haemolytica leukotoxoid mutants expressing Mycoplasma antigens are highly effective against M. bovis infections in cattle in a controlled setting.