Enhancement of mucosal enterovirus vaccine immune response with Flt3L protein or Flt3L-VP1 fusion gene.
Date Issued
2007
Date
2007
Author(s)
Lin, Szu-Wei
DOI
en-US
Abstract
Enterovirus 71 infects many children and adults and and might result in mortality in Taiwan every year. It is important to develop vaccine for protection against enterovivus infection. Flt3 (fms-like tyrosine kinase 3) ligand is an important hematopoietic cytokine. Recent studies suggested that in vivo Flt3L treatment of mice and human volunteers resulted in dramatic increases in the number of functional dendritic cells in bone marrow, spleen, thymus, and various lymphoid tissues. As a result, we tried to apply Flt3L as the adjuvant for enhancing the immunogenecity of antigen. According to our previous result, we found that delivery of plasmids containing flt3l and plasmids containing vp1 to BALB/c mice could elicit serum VP1-specific antibodies. In this study, we tried to construct a fusion protein of adjuvant Flt3L and antigen VP1. In vitro functional assay showed that the fusion protein alone could stimulate dendritic cell differentiation and maturation as treatment of IL-4 and GM-CSF could. Therefore, we tried to enhance EV71 vaccine efficiency on BALB/c mice via intranasal delivery of fl-vp1 fusion gene and FL protein combined with VP1 protein.The results showed that both vaccine strategies could elicit high titer of specific antibodies. The neutralization titers of some experimental groups were better than positive groups and the antibodies in sera had protection against enterovirus infection. We also found that in DNA vaccines, the effect of fusion gene was better than individual genes and protein vaccines were more effective than DNA vaccines. Thus, it was suggested that Flt3L could be a good and potent vaccine adjuvant, probably more potential than cholera toxin in enterovirus vaccine development. In the future, we may apply Flt3L combined with virus-like particles or other enterovirus capsid proteins to search a better vaccine candidate.
Subjects
腸病毒
疫苗
Enterovirus
vaccine
SDGs
Type
other
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