Imperial College London
Alternate

ProfessorRobinShattock

Faculty of Medicine, Department of Infectious Disease

Chair in Mucosal Infection and Immunity
 
 
 
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Contact

 

+44 (0)20 7594 5206r.shattock

 
 
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Location

 

453Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mann:2022:10.1111/imm.13429,
author = {Mann, JFS and McKay, PF and Klein, K and Pankrac, J and Tregoning, JS and Shattock, RJ},
doi = {10.1111/imm.13429},
journal = {Immunology},
pages = {301--311},
title = {Blocking T-cell egress with FTY720 extends DNA vaccine expression but reduces immunogenicity},
url = {http://dx.doi.org/10.1111/imm.13429},
volume = {165},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 disconnect between transgene expression and immunogenicity, as increasing expression by this approach did not enhance the overall immune response. Furthermore, when FTY720 was administered alongside a DNA vaccine expressing the HIV gp140 envelope antigen, there was a significant reduction in both antigen-specific antibody and T-cell responses. This indicates that the developing antigen-specific cellular response clears DNA vaccine expression but requires access to the site of expression in order to develop an effective immune response.
AU  - Mann,JFS
AU  - McKay,PF
AU  - Klein,K
AU  - Pankrac,J
AU  - Tregoning,JS
AU  - Shattock,RJ
DO  - 10.1111/imm.13429
EP  - 311
PY  - 2022///
SN  - 0019-2805
SP  - 301
TI  - Blocking T-cell egress with FTY720 extends DNA vaccine expression but reduces immunogenicity
T2  - Immunology
UR  - http://dx.doi.org/10.1111/imm.13429
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000729281200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://onlinelibrary.wiley.com/doi/10.1111/imm.13429
UR  - http://hdl.handle.net/10044/1/93758
VL  - 165
ER  -
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