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Blocking T‐cell egress with FTY720 extends DNA vaccine expression but reduces immunogenicity by Jamie F. S. Mann; Paul F. McKay; Katja Klein; Joshua Pankrac; John S. Tregoning; Robin J. Shattock is a Immunology and Microbiology article available to read on EtoBox.

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## Abstract Optimal immunogenicity from nucleic acid vaccines requires a balance of antigen expression that effectively engages the host immune system without generating a cellular response that rapidly destroys cells producing the antigen and thereby limiting vaccine antigen expression. We investigated the role of the cellular response on the expression and antigenicity of DNA vaccines using a plasmid DNA construct expressing luciferase. Repeated intramuscular administration led to diminished luciferase expression, suggesting a role for immune‐mediated clearance of expression. To investigate the role of cell trafficking, we used the sphingosine 1‐phosphate receptor (S1PR) modulator, FTY720 (Fingolimod), which traps lymphocytes within the lymphoid tissues. When lymphocyte trafficking was blocked with FTY720, DNA transgene expression was maintained at a constant level for a significantly extended time period. Both continuous and staggered administration of FTY720 prolonged transgene expression. However, blocking lymphocyte egress during primary transgene administration did not result in an increase of transgene expression during secondary administration. Interestingly, there was a d

Who reads Blocking T‐cell egress with FTY720 extends DNA vaccine expression but reduces immunogenicity?

Author

Jamie F. S. Mann; Paul F. McKay; Katja Klein; Joshua Pankrac; John S. Tregoning; Robin J. Shattock

Publisher

Wiley

Published

2021

Language

EN

Field

Immunology and Microbiology (Life Sciences)