Vaccination with DNA vaccines encoding MPB70 or MPB83 or a MPB70 DNA prime-protein boost does not protect cattle against bovine tuberculosis.
METHODS
Bovine tuberculosis is a problem in a number of countries and protection of cattle by vaccination could be an important control strategy.


OBJECTIVE
To determine the ability of DNA vaccines, which express the mycobacterial antigens MPB83 and MPB70 and a DNA prime-protein boost strategy to stimulate immune responses in cattle and protect against bovine tuberculosis.


METHODS
Groups of cattle (n=10) were vaccinated with MPB83 DNA, MPB70 DNA, or MPB70 DNA followed by MPB70 protein or injected with BCG or control plasmid DNA. Animals were challenged intratracheally with virulent Mycobacterium bovis at 13 weeks and protection assessed 17 weeks later at postmortem.


RESULTS
In contrast to the strong cellular immune responses induced by BCG, the DNA vaccines induced minimal interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) responses. Cattle primed with MPB70 DNA and boosted with MPB70 protein induced a strong antibody response and a weak IFN-gamma response. BCG gave significant reduction in four pathological parameters of disease while the DNA vaccines and MPB70 DNA/protein did not protect animals against challenge with M. bovis. Moreover, cattle vaccinated with MPB70 DNA/protein had a significantly higher proportion of animals with severe lung lesions (>100 lesions) than the MPB70 DNA alone or the control group. Increased bovine PPD-specific IL-4 mRNA expression in cattle, post-challenge, correlated with the presence of tuberculous lung lesions.


CONCLUSIONS
Vaccination of calves with MPB70 or MPB83 DNA vaccines or with a more immunogenic MPB70 DNA prime-protein boost strategy did not induce protection against bovine tuberculosis.
Wedlock
D N
DN
AgResearch, Wallaceville Animal Research Centre, P.O. Box 40063, Upper Hutt, New Zealand. neil.wedlock@agresearch.co.nz
Skinner
M A
MA
Parlane
N A
NA
Vordermeier
H M
HM
Hewinson
R G
RG
de Lisle
G W
GW
Buddle
B M
BM
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D002417:Cattle; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008565:Membrane Proteins / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014380:Tuberculosis, Bovine / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000473:pathology / Q000662:veterinary; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D007376:Interleukin-2; C094904:MPB83 protein, Mycobacterium; D008565:Membrane Proteins; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; C060216:MPB70 protein, Mycobacterium bovis; D015847:Interleukin-4; D007371:Interferon-gamma