GRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for ≥6 months in previously-vaccinated older adults.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 06 2023
06 06 2023
Historique:
received:
27
01
2023
accepted:
22
05
2023
medline:
8
6
2023
pubmed:
7
6
2023
entrez:
6
6
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37280238
doi: 10.1038/s41467-023-39053-9
pii: 10.1038/s41467-023-39053-9
pmc: PMC10242235
doi:
Substances chimiques
GRT-R910 vaccine
0
RNA, Messenger
0
spike protein, SARS-CoV-2
0
Antibodies, Viral
0
Antibodies, Neutralizing
0
Banques de données
ClinicalTrials.gov
['NCT05148962']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3274Informations de copyright
© 2023. The Author(s).
Références
Lancet. 2020 Aug 15;396(10249):467-478
pubmed: 32702298
Nat Commun. 2021 Nov 4;12(1):6379
pubmed: 34737312
EClinicalMedicine. 2022 Feb;44:101262
pubmed: 35043093
Science. 2020 Oct 2;370(6512):89-94
pubmed: 32753554
Clin Infect Dis. 2022 Dec 19;75(12):2079-2087
pubmed: 35521791
Nat Med. 2022 Mar;28(3):490-495
pubmed: 35046573
Nat Med. 2022 Aug;28(8):1619-1629
pubmed: 35970920
Nature. 2022 Aug;608(7923):603-608
pubmed: 35790190
NPJ Vaccines. 2022 Dec 13;7(1):161
pubmed: 36513697
Int J Surg. 2022 Dec;108:106994
pubmed: 36375791
N Engl J Med. 2022 Oct 6;387(14):1332-1333
pubmed: 36103455
N Engl J Med. 2020 Dec 17;383(25):2439-2450
pubmed: 33053279
PLoS One. 2015 Oct 28;10(10):e0141561
pubmed: 26509579
Nature. 2022 Sep;609(7929):998-1004
pubmed: 36131022
Nature. 2022 Jan;601(7891):110-117
pubmed: 34758478
Science. 2021 Dec 03;374(6572):abm0829
pubmed: 34648302
BMJ. 2022 Oct 3;379:e072141
pubmed: 36191948
JAMA. 2022 Oct 18;328(15):1559-1561
pubmed: 36149677
Lancet. 2021 Dec 18;398(10318):2258-2276
pubmed: 34863358
Nat Commun. 2022 Jun 7;13(1):3289
pubmed: 35672369
Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14604-9
pubmed: 22908294
N Engl J Med. 2020 Oct 15;383(16):1544-1555
pubmed: 32722908
Lancet. 2021 Oct 16;398(10309):1407-1416
pubmed: 34619098
Mol Ther. 2021 Jun 2;29(6):1970-1983
pubmed: 33823303
N Engl J Med. 2022 May 5;386(18):1712-1720
pubmed: 35381126
J Med Virol. 2022 Apr;94(4):1641-1649
pubmed: 34914115
Cell. 2020 Jun 25;181(7):1489-1501.e15
pubmed: 32473127
Adv Drug Deliv Rev. 2021 Sep;176:113900
pubmed: 34324884
Lancet. 2021 Dec 4;398(10316):2093-2100
pubmed: 34756184
Mol Ther. 2018 Feb 7;26(2):446-455
pubmed: 29275847
J Med Virol. 2022 Jul;94(7):2939-2961
pubmed: 35229324
China CDC Wkly. 2021 Dec 3;3(49):1049-1051
pubmed: 34934514
Cell. 2021 Aug 19;184(17):4401-4413.e10
pubmed: 34265281
Front Immunol. 2021 Jan 15;11:604591
pubmed: 33519813
Nat Immunol. 2022 Feb;23(2):186-193
pubmed: 35105982
N Engl J Med. 2021 Dec 9;385(24):e84
pubmed: 34614326
Nat Med. 2022 Sep;28(9):1785-1790
pubmed: 35760080
Methods Mol Biol. 2005;302:51-86
pubmed: 15937345
Front Immunol. 2021 Dec 06;12:758294
pubmed: 34938287
N Engl J Med. 2021 Nov 4;385(19):1761-1773
pubmed: 34525277
Med Microbiol Immunol. 2023 Feb;212(1):25-34
pubmed: 36370196
Nat Commun. 2022 Jan 10;13(1):80
pubmed: 35013199
Nature. 2021 Feb;590(7847):630-634
pubmed: 33276369
Hum Immunol. 2007 Sep;68(9):779-88
pubmed: 17869653
Nat Biotechnol. 2018 Dec 17;:
pubmed: 30556813
Science. 2022 Jan 07;375(6576):43-50
pubmed: 34812653
J Infect. 2022 Jun;84(6):795-813
pubmed: 35405168
Nature. 2022 Jan;601(7894):617-622
pubmed: 34814158
JCI Insight. 2022 May 23;7(10):
pubmed: 35439174
N Engl J Med. 2020 Dec 17;383(25):2427-2438
pubmed: 32991794
Nature. 2021 Apr;592(7853):283-289
pubmed: 33524990
Science. 2020 Jul 17;369(6501):330-333
pubmed: 32366695
Nat Immunol. 2020 Nov;21(11):1336-1345
pubmed: 32887977
Cell Rep Med. 2021 Feb 16;2(2):100204
pubmed: 33521695
Sci Transl Med. 2010 Sep 1;2(47):47ra64
pubmed: 20811043
Science. 2021 Sep 17;373(6561):1372-1377
pubmed: 34385356