Efficacy and immunogenicity of Mycobacterium bovis DeltaRD1 against aerosol M. bovis infection in neonatal calves.
An attenuated Mycobacterium bovisRD1 deletion (DeltaRD1) mutant of the Ravenel strain was constructed, characterized, and sequenced. This M. bovis DeltaRD1 vaccine strain administered to calves at 2 weeks of age provided similar efficacy as M. bovis bacillus Calmette Guerin (BCG) against low dose, aerosol challenge with virulent M. bovis at 3.5 months of age. Approximately 4.5 months after challenge, both DeltaRD1- and BCG-vaccinates had reduced tuberculosis (TB)-associated pathology in lungs and lung-associated lymph nodes and M. bovis colonization of tracheobronchial lymph nodes as compared to non-vaccinates. Mean central memory responses elicited by either DeltaRD1 or BCG prior to challenge correlated with reduced pathology and bacterial colonization. Neither DeltaRD1 or BCG elicited IFN-gamma responses to rESAT-6:CFP-10 prior to challenge, an emerging tool for modern TB surveillance programs. The DeltaRD1 strain may prove useful for bovine TB vaccine programs, particularly if additional mutations are included to improve safety and immunogenicity.
Waters
W Ray
WR
National Animal Disease Center, Agricultural Research Service, US Department of Agriculture, Ames, IA 50010, USA. ray.waters@ars.usda.gov
Palmer
Mitchell V
MV
Nonnecke
Brian J
BJ
Thacker
Tyler C
TC
Scherer
Charles F Capinos
CF
Estes
D Mark
DM
Hewinson
R Glyn
RG
Vordermeier
H Martin
HM
Barnes
S Whitney
SW
Federe
Glenn C
GC
Walker
John R
JR
Glynne
Richard J
RJ
Hsu
Tsungda
T
Weinrick
Brian
B
Biermann
Karolin
K
Larsen
Michelle H
MH
Jacobs
William R
WR
D000336:Aerosols; D000818:Animals; D000831:Animals, Newborn; D002417:Cattle; D015169:Colony Count, Microbial; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D007156:Immunologic Memory; D008168:Lung / Q000473:pathology; D008198:Lymph Nodes / Q000382:microbiology / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009163:Mycobacterium bovis / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D016019:Survival Analysis; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D014380:Tuberculosis, Bovine / Q000276:immunology / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology
D000336:Aerosols; D004269:DNA, Bacterial; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated