Characterization of the Cellular Immune Response to TonB-Dependent Proteins of Histophilus somni in Murine and Cattle Models

Abstract

Histophilus somni is an economically important member of the bovine respiratory disease (BRD) complex. An H. somni infection has a number of clinical manifestations including septicemia, myocarditis, pneumonia, bronchopneumonia, arthritis and infectious thromboembolic meningoencephalitis. The incidence of systemic disease has significantly increased over the past decade while respiratory disease incidence has remained constant. Current vaccines based on decades old strains are less effective against the systemic form of disease. An understanding of the immune responses generated as well as the antigens expressed during infection is essential in producing effective vaccines. TonB-dependent proteins have been shown to be protective in other members of the Pastuerellaceae family. Therefore, I hypothesized that vaccination with H. somni TonB-dependent proteins would be protective against experimental infection and a good cellular immune response would be induced following immunization. The genes coding for the TonB-dependent receptor 1372, transferrin-binding protein 1 (Tbp1) and transferrin binding protein 2 (Tbp2) also known as TbpA and TbpB respectively, were cloned, expressed and protein products purified. Vaccine formulations containing all three proteins were tested in mice to determine the Th1/Th2 response. These results showed that Tbp2 induced an increase in the production of IFNγ, a cytokine of the cellular immune response. ELISAs and proliferation assays were used to evaluate whether experimentally infected cattle immunized with the three proteins generated both humoral and cellular immune responses. Results suggested that TonB-dependent receptor 1372 initiates both a proliferative response and a humoral response while Tbp1 and Tbp2 induce a cellular and humoral immune response, respectively, in cattle. This work provides a better understanding of the immune responses generated against H. somni infection and aids in the development of a vaccine capable of preventing both respiratory and systemic disease.