Abstract
To increase the potency of human papillomavirus (HPV) DNA vaccines, we constructed a series of HPV16 L1 vaccines genetically fused with a secretion signal and/or immune cell-recruiting RANTES. The DNA vaccines encoding secretory HPV L1 were constructed by inserting HPV L1 gene into a vector with an ER-targeting secretory signal sequence. The expression plasmid encoding secretory HPV L1 (pER/L1) was fused with cDNA of RANTES, generating pER/L1/R. For comparison, HPV L1 genes were cloned into pVAX1 vector with no signal sequence (pL1), and further linked to the N-terminus (pL1/R) or C-terminus of RANTES (pR/L1). The secretion of L1 proteins was observed in the pER/L1, pER/L1/R, and pR/L1-transfected cells, except the pL1/R-transfected group. Cytoplasmic localization of L1 protein was observed in the cells transfected with pL1/R, but not with pER/L1/R at 48 h after transfection. In mice, RANTES-fused vaccines more effectively elicited the levels of HPV16 L1-specific IgG and IgG2a antibodies than pL1. Of RANTES-fused vaccines, pER/L1/R encoding the secreted fusion protein induced the highest humoral and CD8+ T-cell-stimulating responses. These results suggest that the immunogenicity of HPV L1 DNA vaccines could be enhanced by genetic fusion to a chemokine and secretory signal peptide sequences.
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This work was supported by Korea Research Foundation Grant (KRF 2001-015-FP0128).
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Kim, S., Lee, C., Lee, S. et al. Enhanced immunogenicity of human papillomavirus 16 L1 genetic vaccines fused to an ER-targeting secretory signal peptide and RANTES. Gene Ther 10, 1268–1273 (2003). https://doi.org/10.1038/sj.gt.3301997
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DOI: https://doi.org/10.1038/sj.gt.3301997