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Title: Immune response in mice and swine to DNA vaccines derived from the Pasteurella multocida toxin gene

Author
item Register, Karen
item Sacco, Randy
item Brockmeier, Susan

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/2/2007
Publication Date: 6/8/2007
Citation: Register, K.B., Sacco, R.E., Brockmeier, S. 2007. Immune response in mice and swine to DNA vaccines derived from the Pasteurella multocida toxin gene. Vaccine. 25(32):6118-28.

Interpretive Summary: Currently available Pasteurella multocida vaccines for use in swine do not induce optimal levels of antibody specific for the P. multocida toxin (PMT), the major virulence factor and protective immunogen in atrophic rhinitis. The technical difficulty and expense of large-scale purification of PMT preclude its widespread use as a stand-alone vaccine or as an additive to traditional bacterin vaccines. DNA vaccine technology is an attractive alternative with the potential to overcome these limitations. This study evaluated several potential PMT-specific DNA vaccines and identified one that elicits optimal antibody responses in mice and swine. Subsequent infection of immunized pigs with P. multocida further enhanced antibody responses. PMT-specific antibody levels in pigs immunized with the DNA vaccine were significantly higher than levels found in pigs immunized with a commercially available bacterin vaccine for atrophic rhinitis. Additional studies will evaluate the ability of this DNA vaccine to provide protection against disease in pigs challenged with P. multocida.

Technical Abstract: DNA vaccines were constructed with either a 5’-truncated or full-length, genetically detoxified toxin gene from Pasteurella multocida and two different DNA vaccine vectors, distinguished by the presence or absence of a secretion signal sequence. Optimal PMT-specific antibody responses and spleen cell secretion of interferon-alpha following immunization of mice were achieved with pMM4, the construct containing a signal sequence and encoding the entire toxin. Antibody responses were also induced in pigs immunized with pMM4 and levels increased significantly following booster injections and experimental infection with P. multocida. Significantly increased expression of interferon-alpha was detected in only a small subset of pMM4-immunized pigs. This report documents, for the first time, the ability of a DNA vaccine to elicit immune responses to the P. multocida toxin in both mice and swine.