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

• Published in: Nature communications 2023-06, Vol.14 (1), p.3274-3274, Article 3274
• Main Authors: Palmer, Christine D., Scallan, Ciaran D., Kraemer Tardif, Lauren D., Kachura, Melissa A., Rappaport, Amy R., Koralek, Daniel O., Uriel, Alison, Gitlin, Leonid, Klein, Joshua, Davis, Matthew J., Venkatraman, Harshni, Hart, Meghan G., Jaroslavsky, Jason R., Kounlavouth, Sonia, Marrali, Martina, Nganje, Charmaine N., Bae, Kyounghwa, Yan, Tiffany, Leodones, Katharyn, Egorova, Milana, Hong, Sue-Jean, Kuan, Jenchun, Grappi, Silvia, Garbes, Pedro, Jooss, Karin, Ustianowski, Andrew
• Format: Article
• Language: English
• Subjects: 13/106; 13/21; 13/31; 631/250/255/2514; 631/250/590/2293; 631/326/596/4130; Adults; Aged; Aged, 80 and over; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Clinical Trials as Topic; COVID-19; COVID-19 - prevention & control; Dosage; Enzyme-linked immunosorbent assay; Epitopes; Female; Humanities and Social Sciences; Humans; Humoral immunity; Immunity; Immunogenicity; Immunoglobulin G; Lymphocytes; Lymphocytes T; Male; Middle Aged; Morbidity; mRNA; multidisciplinary; Neutralization; Older people; RNA, Messenger - genetics; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; T-Lymphocytes - immunology; Vaccines; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-39053-9

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. Palmer et al . present interim findings from their clinical trial; they describe the reactogenicity and immunogenicity results of a self-amplifying mRNA SARS-CoV-2 booster vaccine within an older population (≥60 years of age).