A DNA vaccine against foot-and-mouth disease elicits an immune response in swine which is enhanced by co-administration with interleukin-2.
A plasmid DNA vaccine candidate (pCEIS) encoding two foot-and-mouth disease virus (FMDV) VP1 epitopes (amino acid residues 141-160 and 200-213) has been demonstrated to have the ability to elicit both FMDV-specific T cell proliferation and neutralizing antibody against FMD in swine. In this study, the efficiency of the pCEIS DNA vaccine when administrated by intramuscularly injection in swine was confirmed, and the immunogenicity of the pCEIS vaccine candidate was found to be enhanced through co-administration with a newly constructed plasmid (pIL2S) encoding the swine interleukin-2 (IL-2) cDNA. The expression of the pIL2S plasmid was driven by a CMV promotor provided by a pcDNA3.1 vector. Swine IL-2 cDNA was cloned by RT-PCR from swine spleen cells. The pIL2S plasmid was expressed in COS-7 cells after 24 and 96h of transfection in vitro. In an animal trial, results from T cell proliferation assay indicated that the stimulation index (SI) in response to stimulation of FMDV proteins in the swine groups injected with pCEIS plus pIL2S (SI ranging from 9.9 to 15.5) were significantly higher than that with pCEIS alone (SI ranging from 3.3 to 6.6). However, there was no significant difference in FMDV-neutralizing antibody level detected in these two swine groups. Mouse protection tests (MPTs) showed that the blood sera from immunized swine injected with either pCEIS alone or pCEIS plus pIL2S were able to protect suckling mice from FMDV challenge, with protection levels ranging from 10(1) to 10(2) lethal dose 50 (LD(50)) M. In a direct FMDV challenge, all swines immunized with either pCEIS plus pIL2S or with pCEIS alone were challenged with 50LD(50)S (50 x lethal dosage in swine) of FMDV. The animals were fully protected (100%) from the FMD viral challenge. These results suggest that co-administration of the plasmids, pCEIS and pIL2S, enhances of the immunogenicity of the pCEIS DNA vaccine candidate, and both intramuscular injection of pCEIS alone and co-administration of the vaccine candidate with pIL2S can protect the swine from direct FMD challenge.
Wong
Ho Tsun
HT
Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Cheng
Samuel Chak-Sum
SC
Sin
Fion Wan-Yee
FW
Chan
Ella Wai-Ching
EW
Sheng
Zu Tian
ZT
Xie
Yong
Y
D000818:Animals; D000833:Animals, Suckling; D000914:Antibodies, Viral / Q000097:blood; D005537:Aphthovirus / Q000235:genetics / Q000276:immunology*; D019556:COS Cells; D000939:Epitopes / Q000276:immunology; D005536:Foot-and-Mouth Disease / Q000276:immunology / Q000517:prevention & control*; D007273:Injections, Intramuscular; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007928:Lethal Dose 50; D008213:Lymphocyte Activation; D051379:Mice; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013552:Swine; D013553:Swine Diseases / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage*
D000914:Antibodies, Viral; D000939:Epitopes; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014765:Viral Vaccines