Evidence map›Paper›PMID 34990810›Full record

Trial reportMolecular therapy : the journal of the American Society of Gene Therapy2022

A self-amplifying mRNA SARS-CoV-2 vaccine candidate induces safe and robust protective immunity in preclinical models.

Giulietta Maruggi, Corey P Mallett, Jason W Westerbeck, Tiffany Chen, Giuseppe Lofano, Kristian Friedrich, Lin Qu, Jennifer Tong Sun, Josie McAuliffe, Amey Kanitkar and 26 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04758962 (A Phase I, First-Time-in Human), which is not on this map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
7.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04758962 phase1completednot on this map

A Phase I, First-Time-in Human (FTiH), Open-label, Dose Escalation, Non-randomized Study to Assess Safety, Reactogenicity and Immune Response of a CoV-2 SAM (LNP) Vaccine When Administered Intramuscularly on a 0, 1 Month Schedule in Healthy Adults 18 to 50 Years of Age

TypeinterventionalSponsorGlaxoSmithKlineRan2021 to 2022Enrolled10ConditionsVirus DiseasesArms1 µg CoV2 SAM (LNP)
3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 81 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. iScience · 2026
    Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Immunology of RNA-based vaccines: The critical interplay between inflammation and expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors at 5 institutions in 3 countries.

Giulietta MaruggiGSK, Rockville, MD 20850, USA. Electronic address: giulietta.x.maruggi@gsk.com.
Corey P MallettGSK, Rockville, MD 20850, USA.
Jason W WesterbeckGSK, Rockville, MD 20850, USA.
Tiffany ChenGSK, Rockville, MD 20850, USA.
Giuseppe LofanoGSK, Rockville, MD 20850, USA.
Kristian FriedrichGSK, Rockville, MD 20850, USA.
Lin QuGSK, Rockville, MD 20850, USA.
Jennifer Tong SunGSK, Rockville, MD 20850, USA.
Josie McAuliffeGSK, Rockville, MD 20850, USA.
Amey KanitkarGSK, Rockville, MD 20850, USA.
Kathryn T ArrildtGSK, Rockville, MD 20850, USA.
Kai-Fen WangGSK, Rockville, MD 20850, USA.
Ian McBeeGSK, Rockville, MD 20850, USA.
Deborah McCoyGSK, Upper Providence, PA 19426, USA.
Rebecca TerryGSK, Ware, Hertfordshire SG12 ODP, UK.
Alison RowlesGSK, Ware, Hertfordshire SG12 ODP, UK.
Maia Araujo AbrahimCharles River Laboratories, Laval, QC H7V 4B3, Canada.
Michael A RingenbergGSK, Upper Providence, PA 19426, USA.
Malcolm J GainsCharles River Laboratories, Laval, QC H7V 4B3, Canada.
Catherine SpicklerCharles River Laboratories, Laval, QC H7V 4B3, Canada.
Xuping XieDepatment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Jing ZouDepatment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Pei-Yong ShiDepatment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Taru DuttDepartment of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80521, USA.
Marcela Henao-TamayoDepartment of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80521, USA.
Izabela RaganDepartment of Biomedical Sciences, Colorado State University, Fort Collins, CO 80521, USA.
Richard A BowenDepartment of Biomedical Sciences, Colorado State University, Fort Collins, CO 80521, USA.
Russell JohnsonGSK, Rockville, MD 20850, USA.
Sandra NutiGSK, Rockville, MD 20850, USA.
Kate LuisiGSK, Rockville, MD 20850, USA.
Jeffrey B UlmerGSK, Rockville, MD 20850, USA.
Ann-Muriel SteffGSK, Rockville, MD 20850, USA.
Rashmi JalahGSK, Rockville, MD 20850, USA.
Sylvie BertholetGSK, Rockville, MD 20850, USA.
Alan H StokesGSK, Upper Providence, PA 19426, USA.
Dong YuGSK, Rockville, MD 20850, USA. Electronic address: dyu@dynavax.com.
GlaxoSmithKline (United States) · USColorado State University · USProvidence College · USThe University of Texas Medical Branch at Galveston · USUniversity of Hertfordshire · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

RNA vaccines have demonstrated efficacy against SARS-CoV-2 in humans, and the technology is being leveraged for rapid emergency response. In this report, we assessed immunogenicity and, for the first time, toxicity, biodistribution, and protective efficacy in preclinical models of a two-dose self-amplifying messenger RNA (SAM) vaccine, encoding a prefusion-stabilized spike antigen of SARS-CoV-2 Wuhan-Hu-1 strain and delivered by lipid nanoparticles (LNPs). In mice, one immunization with the SAM vaccine elicited a robust spike-specific antibody response, which was further boosted by a second immunization, and effectively neutralized the matched SARS-CoV-2 Wuhan strain as well as B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta) variants. High frequencies of spike-specific germinal center B, Th0/Th1 CD4, and CD8 T cell responses were observed in mice. Local tolerance, potential systemic toxicity, and biodistribution of the vaccine were characterized in rats. In hamsters, the vaccine candidate was well-tolerated, markedly reduced viral load in the upper and lower airways, and protected animals against disease in a dose-dependent manner, with no evidence of disease enhancement following SARS-CoV-2 challenge. Therefore, the SARS-CoV-2 SAM (LNP) vaccine candidate has a favorable safety profile, elicits robust protective immune responses against multiple SARS-CoV-2 variants, and has been advanced to phase 1 clinical evaluation (NCT04758962).

Indexed as

COVID-19SARS-CoV-2AnimalsAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesCricetinaeHumansLiposomesMiceNanoparticlesRatsRNA, MessengerSpike Glycoprotein, CoronavirusTissue DistributionAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesLipid NanoparticlesLiposomesRNA, MessengerSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2biodistributionefficacyimmunogenicitySARS-CoV-2 vaccineself-amplifying mRNAspike antigentoxicity

Identifiers

PMID34990810
PMCPMC8721936
OpenAlexW4206756749

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.