Investigation of a leukotoxin containing immune stimulating complex (ISCOM) vaccine and early immunization in dairy calves
Antigens in concentrated serum free logarithmic phase culture supernatant of 'Mannheimia haemolytica' serotype A1, were incorporated into ISCOMs. Leukotoxin (Lkt), the major virulence factor of 'M. haemolytica ' A1 and a target antigen to induce protection in calves, was successfully incorporated into ISCOM particles. This was confirmed by binding of monoclonal antibody 601, specific for the neutralizing epitope of the toxin. An initial trial in rabbits demonstrated the immunogenicity of the ISCOM-NsTox vaccine by immunoblot of multiple protein antigens against rabbit sera. Thirteen calves were allocated to four groups by systematic random allocation. Two groups were vaccinated subcutaneously or intranasally with ISCOMs-NsTox at 4 and 6 weeks of age and compared to a group vaccinated with Presponse SQ ® (commercial vaccine) and to unvaccinated controls. A booster consisting of Presponse SQ® at 8 weeks, was performed in all vaccinated groups (except three calves). Sera and nasal secretion samples were analyzed by direct/indirect agglutination, Lkt neutralization assay, IgG ELISA to Lkt in sera, and IgG and IgA ELISAs to Lkt in nasal secretions. Calves vaccinated with ISCOM-NsTox IN had significantly higher titers of IgA antibodies to Lkt in nasal secretions at weeks 6 and 7. Improved vaccines are needed for protection of young calves in the presence of maternal antibodies against 'Mannheimia haemolytica'. Based on the present studies ISCOM-based vaccines show promise to induce active responses in neonatal calves. Further studies are needed to confirm and extend these investigations.