Preparation and evaluation of recombinant pyolysin, fimbriae E and HtaA based protein vaccines against Trueperella pyogenes

Abstract

Trueperella pyogenes (T. pyogenes) could cause zoonotic disease in various mammals, resulting in significant economic losses. Due to the lack of effective vaccine and the emergence of bacterial resistance, there is a big need for new and improved vaccines. In this study, the non-hemolytic pyolysin mutant (PLOW497F), fimbriae E (FimE) and a truncated cell wall protein (HtaA-2) were selected to generate single or multivalent protein vaccines and their efficacies against lethal T. pyogenes challenge were evaluated in a mouse model. The results showed that the levels of specific antibody were significantly higher than the PBS control group after the booster vaccination. Compared to PBS treated mice, vaccinated mice had upregulated expressions of the inflammatory cytokine genes after the first vaccination. There was a downward trend thereafter, but return to the similar or even higher levels after challenge. Furthermore, co-immunization with rFimE or rHtaA-2 could significantly enhance the anti-hemolysis antibodies induced by rPLOW497F. The supplement of rHtaA-2 induced higher agglutinating antibodies compared with single administration with rPLOW497F or rFimE. Apart from these, the pathological lesions of lung were alleviated in rHtaA-2, rPLOW497F or their combinations immunized mice. Notably, immunization with rPLOW497F, rHtaA-2, combinations of rPLOW497F and rHtaA-2 or rHtaA-2 and rFimE completely protected mice from challenge, whereas the PBS immunized mice could not survive past 1 day post challenge. Thus, PLOW497F and HtaA-2 might be useful in developing efficient vaccines to prevent T. pyogenes infection.