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Controlling reactogenicity while preserving immunogenicity from a self-amplifying RNA vaccine by modulating
Jason A Wojcechowskyj1, Robyn M Jong2, Imre Mäger2
1ExcepGen Inc. Emeryville, San Francisco, CA, USA. jwojcechowskyj@gmail.com.
NPJ Vaccines
|April 29, 2025
Summary
Self-amplifying RNA (saRNA) vaccines can cause side effects. A new mRNA (RNAx) co-administered with saRNA vaccines reduces these side effects while maintaining or improving immune responses.
Area of Science:
- Vaccinology
- Molecular Biology
- Immunology
Background:
- Self-amplifying RNA (saRNA) vaccines offer advantages over mRNA vaccines but can cause undesirable side effects at effective doses.
- There is a need to improve the tolerability of saRNA vaccine platforms.
Purpose of the Study:
- To investigate the potential of a novel mRNA construct, RNAx, encoding the Cardiovirus leader protein, to enhance saRNA vaccine tolerability and immunogenicity.
- To assess RNAx's ability to modulate host innate signaling pathways and reduce vaccine-induced reactogenicity.
Main Methods:
- Co-administration of RNAx with saRNA vaccine cargo in human primary cells and murine models.
- Measurement of interferon production, Influenza hemagglutinin (HA) expression, and serum biomarkers of reactogenicity.
- Evaluation of antibody and cellular immune responses post-vaccination.
Main Results:
- RNAx reduced interferon production and enhanced HA expression in vitro.
- Co-administration of RNAx with saRNA-LNP vaccines significantly decreased serum biomarkers of reactogenicity in vivo.
- RNAx maintained the magnitude of antibody and cellular responses and consistently enhanced binding antibody titers after a single injection.
Conclusions:
- RNAx, encoding the Cardiovirus leader protein, is a promising platform strategy for improving the tolerability of saRNA-LNP vaccines.
- RNAx can preserve or enhance vaccine immunogenicity while mitigating undesirable side effects, supporting its potential clinical application.
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