Expression Of A T-cell Immunogen And Its Immunological Enhancement On The Vaccines Of Foot-and Mouth Disease

Foot-and-mouth disease virus (FMDV) represents one of the most devastating viruses affecting cloven-hoofed livestock including cattle, sheep, goats and pigs. Foot-and-mouth disease(FMD)ranks first in the A list of infectious diseases of animals, according to the Office International des Epizooties (OIE)and it contributes to severe economic problems of many developing countries. FMDV belongs to the aphthovirus genus of the Picornaviridae family and there are seven serotypes(A, O, C, Asia1, SAT 1, SAT 2 and SAT3) and innumerable subtypes of this virus. Moreover, immunity to one serotype does not provide protection against the others. FMDV shows low immunogenocity and high antigenic variation with high mutation rate which lead to the consequences that current vaccines provide only short-term protection, sometimes lead to incomplete inactivation, which is considered as a risk to massively employ the conventional vaccines that only stimulate limited immune response. Thus, it is crucial to develop alternative vaacines.Upon infection, FMDV elicits a rapid and broad spectrum of immune mechanisms, including humoral and cellular responses. T cell epitopes are presented, associated with MHC class II molecules, to CD4 T lymphocytes on the surface of antigen presenting cells. Activated CD4 T cells can cooperate to an efficient production of anti-viral antibodies by B lymphocytes (associated with protection to FMD), previously activated by its interaction with B cell epitopes present on viral proteins. Thus, it appears that the T cell responses mediated by CD4+ cells are required for protective immunity against FMDV, by participating in the production of antiviral antibodies and by maintaining the appropriate microenvironment needed for a synergistic immune response. Based on these pivotal information, we designed and expressed a T cell immunogen, expecting this T cell immunogen could greatly enhance the immunogenicity of current inactivated vaccine as a novel adjuvant. Meanwhile, the obtained results may pave the way towards design of subunit vaccine of foot-and-mouth disease.In this work, we have investigated the enhanced immune response elicited by a recombinant T cell immunogen as an effective cellular immune adjuvant. The T cell immunogen named TI, which contains several T cell epitopes from the VP1, VP4, 3A and 3D proteins of foot-and-mouth disease virus(FMDV)and two pan-T helper (TH) cell site to broaden the immunogenicity of the protein. Meanwhile, another fusion protein named OAVP1 was expressed in bacteria, which contains two VP1 proteins of O and Asia1 type FMDV. Mice were vaccinated with commercially inactivated vaccine or OAVP1 protein with or without the TI immunogen. The results show that mice inoculated with inactivated vaccine or OAVP1 protein supplemented with TI immunogen produced significantly higher level of neutralizing antibodies (P<0.01 or P<0.05 ) than the mice only inoculated with inactivated vaccine or OAVP1 protein by microneutralization assay; And also an obvious increase in T cell number by flow cytometric analysis and significantly higher concentration of IFN-γsecreted in culture media of spleen lymphocytes were observed in groups supplemented with TI immunogen (P<0.01). From above data, it was demonstrated that TI immunogen expressed was an effective stimulator for humoral and cellular immunity and could help to improve the immunogenicity of inactivated vaccine or protein subunit vaccine.