Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/7/2004
Publication Date: 12/21/2004
Citation: Maue, A.C., Waters, W.R., Palmer, M.V., Whipple, D.L., Minion, F.C., Brown, W.C., Estes, D.M. 2004. Cd80 and cd86 but not cd154 augment dna vaccine-induced protection in experimental bovine tuberculosis. Vaccine. 23(6):769-79. Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, a recent outbreak of tuberculosis in white-tailed deer in Michigan has seriously hindered eradication efforts within the United States. Improved strategies to prevent tuberculosis infection in cattle and wildlife species are needed. In the present study, a novel experimental tuberculosis vaccine was evaluated for efficacy in the prevention of disease associated with experimental infection. Vaccinated cattle had less severe disease than non-vaccinated cattle. These findings indicate that vaccines may be useful for tuberculosis control strategies.
Technical Abstract: DNA vaccination is known to elicit robust cellular and humoral responses to encoded antigen. The co-administration of costimulatory molecules CD80 (B7-1), CD86 (B7-2) and CD154 (CD40L) has been shown to enhance immune responses in several murine models. The role of specific costimulatory molecules in non-rodent species remains incompletely characterized. In these studies, we demonstrate that the co-administration of CD80 and CD86, but not CD154, to an existing candidate subunit DNA vaccine (ESAT-6) against bovine tuberculosis, enhances protection after aerosol challenge with virulent Mycobacterium bovis. Additionally, we have shown that vaccination with M. bovis BCG is protective against tuberculosis following aerosol challenge in cattle. Two independent trials were conducted in cattle to determine the adjuvant effect of encoded antigen + CD80/CD86 and directly compare the adjuvant activities of CD80/CD86 to those of CD154. Co-administration of either CD80/CD86 or CD154 enhanced ESAT-6-specific IFN-g responses as compared to animals vaccinated with ESAT-6 DNA alone. However, following aerosol challenge, only animals vaccinated with CD80/CD86 possessed decreased pathology of the lungs and associated lymph nodes, as measured by gross examination, radiographic lesion morphometry and bacterial recovery. Collectively, these results demonstrate that the co-administration of costimulatory molecules with a protective antigen target enhances bovine immune responses to DNA vaccination, and that CD80/CD86 is superior to CD154 in augmenting DNA vaccine-induced protection in experimental bovine tuberculosis.