TY - JOUR
T1 - Modification of promoter spacer length in vaccinia virus as a strategy to control the antigen expression
AU - Di Pilato, Mauro
AU - Sánchez-Sampedro, Lucas
AU - Mejías-Pérez, Ernesto
AU - Sorzano, Carlos Oscar S.
AU - Esteban, Mariano
N1 - Publisher Copyright:
© 2015 The Authors.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Vaccinia viruses (VACVs) with distinct early promoters have been developed to enhance antigen expression and improve antigen-specific CD8 T-cell responses. It has not been demonstrated how the length of the spacer between the coding region of the gene and its regulatory early promoter motif influences antigen expression, and whether the timing of gene expression can modify the antigen-specific CD4 T-cell response. We generated several recombinant VACVs based on the attenuated modified vaccinia Ankara (MVA) strain, which express GFP or the Leishmania LACK antigen under the control of an optimized promoter, using different spacer lengths. Longer spacer length increased GFP and LACK early expression, which correlated with an enhanced LACK-specific memory CD4 and CD8 T-cell response. These results show the importance of promoter spacer length for early antigen expression by VACV and provide alternative strategies for the design of poxvirus-based vaccines.
AB - Vaccinia viruses (VACVs) with distinct early promoters have been developed to enhance antigen expression and improve antigen-specific CD8 T-cell responses. It has not been demonstrated how the length of the spacer between the coding region of the gene and its regulatory early promoter motif influences antigen expression, and whether the timing of gene expression can modify the antigen-specific CD4 T-cell response. We generated several recombinant VACVs based on the attenuated modified vaccinia Ankara (MVA) strain, which express GFP or the Leishmania LACK antigen under the control of an optimized promoter, using different spacer lengths. Longer spacer length increased GFP and LACK early expression, which correlated with an enhanced LACK-specific memory CD4 and CD8 T-cell response. These results show the importance of promoter spacer length for early antigen expression by VACV and provide alternative strategies for the design of poxvirus-based vaccines.
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U2 - 10.1099/vir.0.000183
DO - 10.1099/vir.0.000183
M3 - Article
C2 - 25972354
AN - SCOPUS:84940186615
SN - 0022-1317
VL - 96
SP - 2360
EP - 2371
JO - Journal of General Virology
JF - Journal of General Virology
IS - 8
ER -