GRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for ≥6 months in previously-vaccinated older adults
Nature Communications·
- DOI
- 10.1038/s41467-023-39053-9
- PMID
- 37280238
- PMCID
- PMC10242235
- OpenAlex
- W4379538311
- Study type
- Journal article
- Publisher
- Springer Science and Business Media LLC
- Article type
- journal-article
- Integrity
- current
Why this research matters now
The vaccine candidate addresses waning humoral immunity observed with authorized vaccines within 6 months of dosing, and targets older populations at higher risk for severe SARS-CoV-2 complications. Durable neutralization and broadened T cell responses may offer extended protection.
Structured evidence summary
Research question
This phase I trial evaluated the safety, tolerability, and immunogenicity of GRT-R910, a self-amplifying mRNA vaccine encoding SARS-CoV-2 Spike and conserved non-Spike T cell epitopes, as a booster in previously vaccinated healthy older adults.
Study design
Open-label dose-escalation phase I trial with interim analysis. Primary endpoints were safety and tolerability; secondary endpoints assessed immunogenicity through IgG binding, neutralization assays, interferon-gamma ELISpot, and intracellular cytokine staining.
Population and setting
Previously vaccinated healthy older adults enrolled in trial NCT05148962.
Main findings
Most solicited adverse events were mild to moderate and transient, with no treatment-related serious adverse events. Neutralizing antibody titers against ancestral and variant Spike were boosted and persisted through at least 6 months, contrasting with authorized vaccines. GRT-R910 increased Spike-specific T cell responses and primed functional responses to conserved non-Spike epitopes.
Public-health relevance
The vaccine candidate addresses waning humoral immunity observed with authorized vaccines within 6 months of dosing, and targets older populations at higher risk for severe SARS-CoV-2 complications. Durable neutralization and broadened T cell responses may offer extended protection.
Important limitations
The study is limited by small sample size. These are interim findings; additional data from ongoing studies are required to corroborate the results.
GIDS interpretation
This article was indexed under SARS, COVID-19, outbreak investigation, treatment, and vaccination topics, reflecting its focus on vaccine development for SARS-CoV-2 in the context of ongoing public health response. The classifier links support discovery of research on immune durability and novel vaccine platforms.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 12 auditable classifier relationships to diseases, places, topics, and study design.