DNA vaccination against foot-and-mouth disease via electroporation: study of molecular approaches for enhancing VP1 antigenicity.
BACKGROUND
Foot-and-mouth disease virus (FMDV) affects susceptible livestock animals and causes disastrous economic impact. Immunization with plasmid expressing VP1 that contains the major antigenic epitope(s) of FMDV as cytoplasmic protein (cVP1) failed to elicit full protection against FMDV challenge.


METHODS
In this study, mice were immunized via electroporation with four cDNA expression vectors that were constructed to express VP1 of FMDV, as cytoplasmic (cVP1), secreted (sVP1), membrane-anchored (mVP1) or capsid precursor protein (P1), respectively, to evaluate whether expression of VP1 in specific subcellular compartment(s) would result in better immune responses.


RESULTS
Electroporation enhanced immune responses to vectors expressing cVP1 or P1 and expedited the immune responses to vectors expressing sVP1 or mVP1. Immunization of mice via electroporation with mVP1 cDNA was better than sVP1 or cVP1 cDNA in eliciting neutralizing antibodies and viral clearance protection. Vaccination with P1 cDNA, nonetheless, yielded the best immune responses and protection among all four cDNAs that we tested.


CONCLUSIONS
These results suggest that the antigenicity of a VP1 DNA vaccine can be significantly enhanced by altering the cellular localization of the VP1 antigen. Electroporation is a useful tool for enhancing the immune responses of vectors expressing VP1 or P1. By mimicking FMDV more closely than that of transgenic VP1 and eliciting immune responses favorably toward Th2, transgenic P1 may induce more neutralizing antibodies and better protection against FMDV challenge.
Kim
Suk-Am
SA
Institute of BioAgricultural Sciences, Academia Sinica, Taipei, Taiwan, ROC.
Liang
Chi-Ming
CM
Cheng
Ivan-Chen
IC
Cheng
Yung-Chih
YC
Chiao
Ming-Tsang
MT
Tseng
Chia-Jen
CJ
Lee
Fan
F
Jong
Ming-Hwa
MH
Tao
Mi-Hua
MH
Yang
Ning-Sun
NS
Liang
Shu-Mei
SM
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000235:genetics; D001483:Base Sequence; D036022:Capsid Proteins / Q000235:genetics* / Q000276:immunology*; D002460:Cell Line; D006224:Cricetinae; D004279:DNA, Viral / Q000235:genetics; D018274:Electroporation; D005260:Female; D005536:Foot-and-Mouth Disease / Q000276:immunology / Q000517:prevention & control*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics* / Q000276:immunology*; D015870:Gene Expression; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics
D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D004279:DNA, Viral; D011994:Recombinant Proteins; C442501:VP1 protein, Foot-and-mouth disease virus; D019444:Vaccines, DNA; D014765:Viral Vaccines