Blocking T-cell egress with FTY720 extends DNA vaccine expression but reduces immunogenicity.

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

SUBMITTER: Mann JFS 

PROVIDER: S-EPMC9426614 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature