GRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for ≥6 months in previously-vaccinated older adults
Open accessAbstract
SARS-CoV-2 has resulted in high levels of morbidity and mortality world-wide, and severe complications can occur in older populations. Humoral immunity induced by authorized vaccines wanes within 6 months, and frequent boosts may only offer transient protection. GRT-R910 is an investigational self-amplifying mRNA (samRNA)-based SARS-CoV-2 vaccine delivering full-length Spike and selected conserved non-Spike T cell epitopes. This study reports interim analyses for a phase I open-label dose-escalation trial evaluating GRT-R910 in previously vaccinated healthy older adults (NCT05148962). Primary endpoints of safety and tolerability were assessed. Most solicited local and systemic adverse events (AEs) following GRT-R910 dosing were mild to moderate and transient, and no treatment-related serious AEs were observed. The secondary endpoint of immunogenicity was assessed via IgG binding assays, neutralization assays, interferon-gamma ELISpot, and intracellular cytokine staining. Neutralizing antibody titers against ancestral Spike and variants of concern were boosted or induced by GRT-R910 and, contrasting to authorized vaccines, persisted through at least 6 months after the booster dose. GRT-R910 increased and/or broadened functional Spike-specific T cell responses and primed functional T cell responses to conserved non-Spike epitopes. This study is limited due to small sample size, and additional data from ongoing studies will be required to corroborate these interim findings.
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In a small phase 1 trial reported in 2023, another saRNA vaccine elicited neutralising antibodies and T-cell responses against SARS-CoV-2 D614G strain and beta, delta, and omicron variants in older adults (≥60 years) previously immunised with ChAdOx1 nCoV-19 vaccine, and the boost persisted for at least 6 months.
“However, in a small phase 1 trial reported in 2023, another saRNA vaccine elicited neutralising antibodies and T-cell responses against SARS-CoV-2 D614G strain and beta, delta, and omicron variants in older adults (aged ≥60 years) who had previously been immunised with the adenovirus-vectored ChAdOx1 nCoV-19 vaccine.25 Furthermore, this boost in immunity was shown to persist for at least 6 months.”
From Immunogenicity and safety of a booster dose of a self-amplifying RNA COVID-19 vaccine (ARCT-154) versus BNT162b2 mRNA COVID-19 vaccine: a double-blind, multicentre, randomised, controlled, phase 3, non-inferiority trial (2024) · cites this paper as [25]
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- Authors
- Palmer, C. D., Scallan, C. D., Kraemer Tardif, L. D., Kachura, M. A., Rappaport, A. R., Koralek, D. O., Uriel, A., Gitlin, L., Klein, J., Davis, M. J., Venkatraman, H., Hart, M. G., Jaroslavsky, J. R., Kounlavouth, S., Marrali, M., Nganje, C. N., Bae, K., Yan, T., Leodones, K., Egorova, M., Hong, S.-J., Kuan, J., Grappi, S., Garbes, P., Jooss, K., & Ustianowski, A.
- Affiliations
- North Manchester General Hospital (GB)
- VisMederi (Italy) (IT)
- Corresponding author
- Jooss, Karin
- ORCID
- Venue
- Nature Communications
- Published
- 2023-06-06
- Volume
- 14
- Issue
- 1
- Pages
- 3274-3274
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10242235
- OpenAlex
- W4379538311
- Cited by
- 42
- References
- 58
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 13 · 2023: 2 · 2013: 1
- FWCI
- 8.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Coalition for Epidemic Preparedness Innovations
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- self-amplifying mRNA vaccine, SARS-CoV-2, COVID-19 vaccines, booster vaccination, older adults, immunogenicity, neutralizing antibodies, T cell response, vaccine safety, dose escalation, antibody waning
- MeSH terms
- COVID-19, COVID-19 Vaccines, mRNA Vaccines, Aged, Aged, 80 and over, Antibodies, Viral, Clinical Trials as Topic, Female, Humans, Male, Middle Aged, RNA, Messenger, T-Lymphocytes, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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