Modulation of bovine immune responses to genetic immunization

Genetic immunization elicits robust humoral and cell-mediated immune responses to encoded antigen. It has been difficult to generate comparable responses in non-rodent species. Three independent trials were conducted in cattle to determine the adjuvant effects of plasmid-encoded CD80/CD86 or CD154 co-administered with CpG ODN, and granulocyte macrophage-colony stimulating factor on DNA vaccines (ESAT-6 and ESAT-6:CFP10) against bovine tuberculosis. Co-administration of CD80/CD86 or CD154 enhanced antigen-specific IFN-gamma responses to ESAT-6 compared to control vaccinates. Following aerosol challenge with Mycobacterium bovis, only animals vaccinated with CD80/CD86 possessed decreased pathology of the lungs and associated lymph nodes. Immunization with an ESAT-6:CFP10 + GM-CSF + CD80/CD86 DNA vaccine resulted in enhanced proliferative responses and IFN-gamma production. Efficacy of the ESAT-6:CFP10 + GM-CSF + CD80/CD86 DNA vaccine was not evaluated. Collectively, these results demonstrate that bovine immune responses to genetic immunization can be enhanced following co-administration of molecular adjuvants.