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Infection and Immunity, December 2007, p. 5837-5844, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.00834-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Safety and Protective Efficacy of Intramuscular Vaccination with a Live aroA Derivative of Pasteurella multocida B:2 against Experimental Hemorrhagic Septicemia in Calves{triangledown}

Mark P. Dagleish,1 J. Christopher Hodgson,1 Saeed Ataei,2,{dagger} Anna Finucane,2 Jeanie Finlayson,1 Jill Sales,3 Roger Parton,2 and John G. Coote2*

Moredun Research Institute, International Research Centre, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, United Kingdom,1 Infection and Immunity Division, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom,2 Biomathematics & Statistics Scotland, James Clerk Maxwell Building, The King's Buildings, University of Edinburgh, Edinburgh, United Kingdom3

Received 18 June 2007/ Returned for modification 8 August 2007/ Accepted 5 September 2007

Three groups of five calves, namely, V1, V2, and V3, were immunized intramuscularly at 4 and 8 weeks of age with ca. 109, 108, and 107 CFU, respectively, of a derivative of Pasteurella multocida B:2 wild-type strain 85020 containing a deletion in the aroA gene (strain JRMT12). The first and second vaccinations resulted in significantly (P < 0.01) higher rectal temperature responses in groups V1 and V2 than in group V3. Serum immunoglobulin M (IgM) and IgG titers did not increase in any group until after the second vaccination and were then significantly higher in groups V1 and V2 than in group V3 (P = 0.001 for both IgM and IgG). All vaccinated groups and three unvaccinated challenge control calves (group CC) were injected subcutaneously at 10 weeks of age with ca. 107 CFU of strain 85020. Vaccinated calves survived the challenge, but two CC animals developed clinical disease and were killed for humane reasons. After challenge, mean serum amyloid A concentrations were significantly higher (P < 0.001) in the CC group than in the vaccinated groups. Postmortem examination revealed that calves in the CC group showed the most extensive range of bacteriologically positive tissues and gross and histopathological lesions. Overall, a clear dose-dependent response was present, with those receiving a higher vaccine dose being less affected clinically, bacteriologically, and pathologically by the wild-type challenge. The V2 treatment appeared to give the best combination of high immune response, protection, and safety.

* Corresponding author. Mailing address: Infection and Immunity Division, Institute of Biomedical and Life Sciences, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8TA, United Kingdom. Phone: 44 (0) 141 330 5845. Fax: 44 (0) 141 330 4600. E-mail: j.coote{at}bio.gla.ac.uk

{triangledown} Published ahead of print on 17 September 2007.

Editor: A. Camilli

{dagger} Present address: Razi Vaccine and Serum Research Institute, Karaj, Tehran, Islamic Republic of Iran.

Infection and Immunity, December 2007, p. 5837-5844, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.00834-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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