Imperial College London
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ProfessorCeciliaJohansson

Faculty of Medicine, National Heart & Lung Institute

Professor of Mucosal Immunology
 
 
 
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Contact

 

+44 (0)20 7594 2531c.johansson

 
 
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Location

 

367Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tregoning:2023:10.1016/j.omtn.2022.11.024,
author = {Tregoning, JS and Stirling, DC and Wang, Z and Flight, KE and Brown, JC and Blakney, AK and McKay, PF and Cunliffe, RF and Murugaiah, V and Fox, CB and Beattie, M and Tam, YK and Johansson, C and Shattock, RJ},
doi = {10.1016/j.omtn.2022.11.024},
journal = {Molecular Therapy : Nucleic Acids},
pages = {29--42},
title = {Formulation, inflammation, and RNA sensing impact the immunogenicity of self-amplifying RNA vaccines},
url = {http://dx.doi.org/10.1016/j.omtn.2022.11.024},
volume = {31},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - To be effective, RNA vaccines require both in situ translation and the induction of an immune response to recruit cells to the site of immunization. These factors can pull in opposite directions with the inflammation reducing expression of the vaccine antigen. We investigated how formulation affects the acute systemic cytokine response to a self-amplifying RNA (saRNA) vaccine. We compared a cationic polymer (pABOL), a lipid emulsion (nanostructured lipid carrier, NLC), and three lipid nanoparticles (LNP). After immunization, we measured serum cytokines and compared the response to induced antibodies against influenza virus. Formulations that induced a greater cytokine response induced a greater antibody response, with a significant correlation between IP-10, MCP-1, KC, and antigen-specific antibody titers. We then investigated how innate immune sensing and signaling impacted the adaptive immune response to vaccination with LNP-formulated saRNA. Mice that lacked MAVS and are unable to signal through RIG-I-like receptors had an altered cytokine response to saRNA vaccination and had significantly greater antibody responses than wild-type mice. This indicates that the inflammation induced by formulated saRNA vaccines is not solely deleterious in the induction of antibody responses and that targeting specific aspects of RNA vaccine sensing might improve the quality of the response.
AU  - Tregoning,JS
AU  - Stirling,DC
AU  - Wang,Z
AU  - Flight,KE
AU  - Brown,JC
AU  - Blakney,AK
AU  - McKay,PF
AU  - Cunliffe,RF
AU  - Murugaiah,V
AU  - Fox,CB
AU  - Beattie,M
AU  - Tam,YK
AU  - Johansson,C
AU  - Shattock,RJ
DO  - 10.1016/j.omtn.2022.11.024
EP  - 42
PY  - 2023///
SN  - 2162-2531
SP  - 29
TI  - Formulation, inflammation, and RNA sensing impact the immunogenicity of self-amplifying RNA vaccines
T2  - Molecular Therapy : Nucleic Acids
UR  - http://dx.doi.org/10.1016/j.omtn.2022.11.024
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36589712
UR  - http://hdl.handle.net/10044/1/102043
VL  - 31
ER  -
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