Gene gun DNA immunization of cattle induces humoral and CD4 T-cell-mediated immune responses against the Theileria parva polymorphic immunodominant molecule

Abstract

Theileria parva kills over one million cattle annually in sub-Saharan Africa. Parasite genetic complexity, cellular response immunodominance, and bovine MHC diversity have precluded traditional vaccine development. One potential solution is gene gun (GG) immunization, which enables simultaneous administration of one or more DNA-encoded antigens. Although promising in murine, porcine, and human vaccination trials, bovine GG immunization studies are limited. We utilized the model T. parva antigen, polymorphic immunodominant molecule (PIM) to test bovine GG immunization. GG immunization using a mammalian codon optimized PIM sequence elicited significant anti-PIM antibody and cell-mediated responses in 7/8 steers, but there was no difference between immunized and control animals following T. parva challenge. The results suggest immunization with PIM, as delivered here, is insufficient to protect cattle from T. parva. Nonetheless, the robust immune responses elicited against this model antigen suggest GG immunization is a promising vaccine platform for T. parva and other bovine pathogens.

Clinical Pathology, Immunopathology and Advanced Vaccine Technology in Bovine Theileriosis: A Review

“…For instance, intradermal injection of DNA vaccine elicits a predominate Th1 response, while the so called biological ballistic or biolistic DNA injections mainly stimulate a Th2 or a balanced Th1/Th2 response [ 175 ]. Fry et al [ 176 ] demonstrated for the first time the particle-mediated epidermal delivery of a DNA vaccine whereby a DNA-encoded T. parva codon-optimized and native sequence PIM antigen was delivered through the intra-dermal route in Holstein steers. This method is also known as gene gun immunization, whereby DNA-encoded antigens are delivered directly into the nucleus of epidermal and dermal professional and non-professional antigen-presenting cells.…”

“…The use of gene gun immunization against T. parva infection elicited a robust protective immune response characterized by significant antibody and cell-mediated responses (Th1/IgG2 and INF-γ responses). Although the antibody response mounted was not enough to prevent East Coast fever in the T. parva -challenged calves, gene gun immunization may serve in the future as a suitable vaccine platform against T. parva and other bovine blood pathogens in cattle that sufficiently express the MHC class I molecules, with the role of binding and presenting PIM epitopes to cytotoxic T cells [ 176 ].…”

Changes in the Molecular and Functional Phenotype of Bovine Monocytes during Theileria parva Infection

“…The animals were initially used to establish the baseline results of monocyte phenotyping and functional assays in uninfected cattle. Subsequently, six animals were infected with 1 ml of T. parva sporozoite stabilate (Pullman 2015/4, Muguga strain), as previously described for lethal infection (47), and four cattle were infected with the same parasite stabilate and concomitantly treated intramuscularly with 20 mg/kg of body weight of long-acting oxytetracycline (LA200; Zoetis), as previously described for nonlethal infection (48). Both lethally and nonlethally infected animals were monitored daily for fever, leukopenia, and respiratory distress.…”

Pursuing effective vaccines against cattle diseases caused by apicomplexan protozoa

“…Altogether, these factors indicate that novel and more sustainable vaccines are needed to control ECF. The polymorphic immunodominant molecule (PIM) is a well-characterized protein expressed by both the sporozoite and schizont stages of T. parva and has been evaluated as a vaccine antigen using different delivery platforms [46,47]. Despite eliciting strong humoral and cellular immune responses, PIM vaccination induced no protection.…”