PMID- 37280238
OWN - NLM
STAT- MEDLINE
DCOM- 20230613
LR  - 20230627
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 14
IP  - 1
DP  - 2023 Jun 6
TI  - GRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for >/=6 months 
      in previously-vaccinated older adults.
PG  - 3274
LID - 10.1038/s41467-023-39053-9 [doi]
LID - 3274
AB  - 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.
CI  - (c) 2023. The Author(s).
FAU - Palmer, Christine D
AU  - Palmer CD
AUID- ORCID: 0000-0003-3213-0398
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Scallan, Ciaran D
AU  - Scallan CD
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Kraemer Tardif, Lauren D
AU  - Kraemer Tardif LD
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Kachura, Melissa A
AU  - Kachura MA
AUID- ORCID: 0000-0001-5910-4443
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Rappaport, Amy R
AU  - Rappaport AR
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Koralek, Daniel O
AU  - Koralek DO
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Uriel, Alison
AU  - Uriel A
AD  - North Manchester General Hospital & University of Manchester, Manchester, UK.
FAU - Gitlin, Leonid
AU  - Gitlin L
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Klein, Joshua
AU  - Klein J
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Davis, Matthew J
AU  - Davis MJ
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Venkatraman, Harshni
AU  - Venkatraman H
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Hart, Meghan G
AU  - Hart MG
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Jaroslavsky, Jason R
AU  - Jaroslavsky JR
AUID- ORCID: 0000-0002-9799-2397
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Kounlavouth, Sonia
AU  - Kounlavouth S
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Marrali, Martina
AU  - Marrali M
AUID- ORCID: 0000-0001-5248-1430
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Nganje, Charmaine N
AU  - Nganje CN
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Bae, Kyounghwa
AU  - Bae K
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Yan, Tiffany
AU  - Yan T
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Leodones, Katharyn
AU  - Leodones K
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Egorova, Milana
AU  - Egorova M
AUID- ORCID: 0000-0002-9917-091X
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Hong, Sue-Jean
AU  - Hong SJ
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Kuan, Jenchun
AU  - Kuan J
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Grappi, Silvia
AU  - Grappi S
AD  - VisMederi Srl., Siena, Italy.
FAU - Garbes, Pedro
AU  - Garbes P
AUID- ORCID: 0000-0003-0830-3463
AD  - Gritstone bio, Inc., Emeryville, CA, USA.
FAU - Jooss, Karin
AU  - Jooss K
AUID- ORCID: 0000-0001-7670-4993
AD  - Gritstone bio, Inc., Emeryville, CA, USA. kjooss@gritstone.com.
FAU - Ustianowski, Andrew
AU  - Ustianowski A
AD  - North Manchester General Hospital & University of Manchester, Manchester, UK.
LA  - eng
SI  - ClinicalTrials.gov/NCT05148962
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230606
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (GRT-R910 vaccine)
RN  - 0 (RNA, Messenger)
RN  - 0 (spike protein, SARS-CoV-2)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Antibodies, Neutralizing)
SB  - IM
MH  - RNA, Messenger/genetics
MH  - *COVID-19/prevention & control
MH  - Humans
MH  - Aged
MH  - Male
MH  - Female
MH  - Middle Aged
MH  - Aged, 80 and over
MH  - Clinical Trials as Topic
MH  - Antibodies, Viral/immunology
MH  - Antibodies, Neutralizing/immunology
MH  - T-Lymphocytes/immunology
PMC - PMC10242235
COIS- This study was sponsored by Gritstone bio, Inc. C.D.P., C.D.S., D.O.K., L.D.K.T., 
      A.R.R., M.A.K., L.G., J.K., M.J.D., H.V., M.G.H., J.R.J., S.K., M.M., C.N.N., 
      K.B., T.Y., K.L., M.E., S.-J.H., J.C.K., P.G., and K.J. are stockholders and 
      either current or previous employees at Gritstone bio, Inc. and may be listed as 
      co-inventors on various pending patent applications related to the vaccine 
      platform presented in this study. D.O.K. is currently an employee and shareholder 
      of Gilead sciences. P.G. holds shares in AstraZeneca and Takeda. The remaining 
      authors declare no competing interests. Participants did not receive compensation 
      for participating in this study.
EDAT- 2023/06/07 01:07
MHDA- 2023/06/08 06:42
PMCR- 2023/06/06
CRDT- 2023/06/06 23:18
PHST- 2023/01/27 00:00 [received]
PHST- 2023/05/22 00:00 [accepted]
PHST- 2023/06/08 06:42 [medline]
PHST- 2023/06/07 01:07 [pubmed]
PHST- 2023/06/06 23:18 [entrez]
PHST- 2023/06/06 00:00 [pmc-release]
AID - 10.1038/s41467-023-39053-9 [pii]
AID - 39053 [pii]
AID - 10.1038/s41467-023-39053-9 [doi]
PST - epublish
SO  - Nat Commun. 2023 Jun 6;14(1):3274. doi: 10.1038/s41467-023-39053-9.