GRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for ≥6 months in previously-vaccinated older adults.

Autor: Palmer CD; Gritstone bio, Inc., Emeryville, CA, USA., Scallan CD; Gritstone bio, Inc., Emeryville, CA, USA., Kraemer Tardif LD; Gritstone bio, Inc., Emeryville, CA, USA., Kachura MA; Gritstone bio, Inc., Emeryville, CA, USA., Rappaport AR; Gritstone bio, Inc., Emeryville, CA, USA., Koralek DO; Gritstone bio, Inc., Emeryville, CA, USA., Uriel A; North Manchester General Hospital & University of Manchester, Manchester, UK., Gitlin L; Gritstone bio, Inc., Emeryville, CA, USA., Klein J; Gritstone bio, Inc., Emeryville, CA, USA., Davis MJ; Gritstone bio, Inc., Emeryville, CA, USA., Venkatraman H; Gritstone bio, Inc., Emeryville, CA, USA., Hart MG; Gritstone bio, Inc., Emeryville, CA, USA., Jaroslavsky JR; Gritstone bio, Inc., Emeryville, CA, USA., Kounlavouth S; Gritstone bio, Inc., Emeryville, CA, USA., Marrali M; Gritstone bio, Inc., Emeryville, CA, USA., Nganje CN; Gritstone bio, Inc., Emeryville, CA, USA., Bae K; Gritstone bio, Inc., Emeryville, CA, USA., Yan T; Gritstone bio, Inc., Emeryville, CA, USA., Leodones K; Gritstone bio, Inc., Emeryville, CA, USA., Egorova M; Gritstone bio, Inc., Emeryville, CA, USA., Hong SJ; Gritstone bio, Inc., Emeryville, CA, USA., Kuan J; Gritstone bio, Inc., Emeryville, CA, USA., Grappi S; VisMederi Srl., Siena, Italy., Garbes P; Gritstone bio, Inc., Emeryville, CA, USA., Jooss K; Gritstone bio, Inc., Emeryville, CA, USA. kjooss@gritstone.com., Ustianowski A; North Manchester General Hospital & University of Manchester, Manchester, UK.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jun 06; Vol. 14 (1), pp. 3274. Date of Electronic Publication: 2023 Jun 06.
DOI: 10.1038/s41467-023-39053-9
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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