PROTECTION OF RUMINANTS BY PASTEURELLA-HAEMOLYTICA A1 CAPSULAR POLYSACCHARIDE VACCINES CONTAINING MURAMYL DIPEPTIDE ANALOGS

The capsular polysaccharide (CP) of Pasteurella haemolytica serotype A l is a poor immunogen for the prevention of pneumonic pasteurellosis o f ruminants. To improve CP immunogenicity, vaccines were prepared with 1.0 mg CP dose(-1) with and without the synthetic adjuvant, muramyl d ipeptide (MDP; range 0.2-1.0 mg) or a lipophilic derivative, MDP-sn-gl yceryl-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 wi th CP, antibody titers in lambs and calves were typical of that seen w ith polysaccharide immunogens and characterized by an early IgM respon se followed by later IgG1 and IgG2 responses. CP + MDP or MDP-GDP vacc ines induced significantly higher IgM, IgG1, and IgG2 titers. After tr anstracheal challenge of immunity with P. haemolytica serotype Al, ext ensive pulmonary consolidation containing P. haemolytica (10(6)-10(8) c.f.u. g(-1)) was seen in all lambs and calves vaccinated with CP alon e and was Mot significantly different (P<0.05) from the consolidation and concentrations of organisms in nonvaccinated challenge controls. I n lambs, vaccines containing 1.0 mg: CP+0.05 mg MDP or MDP-GDP signifi cantly reduced pulmonary consolidation and concentrations of P. haemol ytica 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 consoli dation 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 bact ericidal antibodies by 7 days and were move efficacious than two comme rcial vaccines. Potentiation of CP with MDP or MDP-GDP has great promi se in furthering the potential of CP as a vaccine immunogen for the pr evention of pneumonic pasteurellosis.