Systems vaccinology analysis of saRNA immunisation identifies an acute innate immune signature correlated with adaptive immunity.
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Self-amplifying RNA (saRNA) vaccines are a next-generation RNA vaccine platform with great potential. Systems vaccinology provides a potent tool to interrogate vaccine-induced responses in volunteers and to dissect the mechanisms by which vaccines elicit a protective immune response or cause reactogenicity. In the current study, we performed transcriptomic analysis on blood samples collected from volunteers vaccinated as part of a phase I study of an saRNA vaccine expressing SARS-CoV-2 spike antigen. We observed significant gene overexpression following vaccination, both at the prime and boost vaccinations. Over-expressed genes were predominantly associated with type I interferon signalling pathways and associated with innate immune cell recruitment. This
transcriptomic signature was reflected by an increase in cytokines in the plasma at the same timepoint and a significant increase in monocytes in the blood, both of which correlated with the antibody response to the vaccine. When individuals were segregated by the degree of reactogenicity, we also detected differences in gene expression related to immune responses. Overall, this shows that saRNA induces a potent, acute inflammatory response with similarities to other RNA vaccines, it will be important to further dissect the role of the over-expressed genes in immunogenicity and reactogenicity.
transcriptomic signature was reflected by an increase in cytokines in the plasma at the same timepoint and a significant increase in monocytes in the blood, both of which correlated with the antibody response to the vaccine. When individuals were segregated by the degree of reactogenicity, we also detected differences in gene expression related to immune responses. Overall, this shows that saRNA induces a potent, acute inflammatory response with similarities to other RNA vaccines, it will be important to further dissect the role of the over-expressed genes in immunogenicity and reactogenicity.
Date Issued
2026-03-12
Date Acceptance
2026-02-13
Citation
Molecular Therapy: Methods & Clinical Development, 2026, 34 (1)
ISSN
2329-0501
Publisher
Elsevier
Journal / Book Title
Molecular Therapy: Methods & Clinical Development
Volume
34
Issue
1
Copyright Statement
© 2026 The Authors. Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
10.1016/j.omta.2026.201706
Publication Status
Published
Article Number
201706
Date Publish Online
2026-02-20