Evidence map›Paper›PMID 27525409›Full record

ArticlePloS one2016

Self-Amplifying mRNA Vaccines Expressing Multiple Conserved Influenza Antigens Confer Protection against Homologous and Heterosubtypic Viral Challenge.

Diletta Magini, Cinzia Giovani, Simona Mangiavacchi, Silvia Maccari, Raffaella Cecchi, Jeffrey B Ulmer, Ennio De Gregorio, Andrew J Geall, Michela Brazzoli, Sylvie Bertholet

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
7.2field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 127 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. The advent of clinical self-amplifying RNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  5. Article
  6. Research progress of mosquito-borne virus mRNA vaccines.Molecular therapy. Methods & clinical development · 2025
    Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. International journal of molecular sciences · 2024
    Article
  12. Review
  13. Generation and Characterization of In Vitro Transcribed mRNA.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Review

22 more citing papers are in PubMed but not listed here.

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

10 authors at 3 institutions in 2 countries.

Diletta MaginiNovartis Vaccines, S.r.l., Siena, Italy.
Cinzia GiovaniNovartis Vaccines, S.r.l., Siena, Italy.
Simona MangiavacchiNovartis Vaccines, S.r.l., Siena, Italy.
Silvia MaccariNovartis Vaccines, S.r.l., Siena, Italy.
Raffaella CecchiNovartis Vaccines, S.r.l., Siena, Italy.
Jeffrey B UlmerNovartis Vaccines Inc., Cambridge, MA, United States of America.
Ennio De GregorioNovartis Vaccines, S.r.l., Siena, Italy.
Andrew J GeallNovartis Vaccines Inc., Cambridge, MA, United States of America.
Michela BrazzoliNovartis Vaccines, S.r.l., Siena, Italy.
Sylvie BertholetNovartis Vaccines, S.r.l., Siena, Italy.
Novartis (Italy) · ITNovartis (United States) · USUniversity of Siena · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Current hemagglutinin (HA)-based seasonal influenza vaccines induce vaccine strain-specific neutralizing antibodies that usually fail to provide protection against mismatched circulating viruses. Inclusion in the vaccine of highly conserved internal proteins such as the nucleoprotein (NP) and the matrix protein 1 (M1) was shown previously to increase vaccine efficacy by eliciting cross-reactive T-cells. However, appropriate delivery systems are required for efficient priming of T-cell responses. In this study, we demonstrated that administration of novel self-amplifying mRNA (SAM®) vectors expressing influenza NP (SAM(NP)), M1 (SAM(M1)), and NP and M1 (SAM(M1-NP)) delivered with lipid nanoparticles (LNP) induced robust polyfunctional CD4 T helper 1 cells, while NP-containing SAM also induced cytotoxic CD8 T cells. Robust expansions of central memory (TCM) and effector memory (TEM) CD4 and CD8 T cells were also measured. An enhanced recruitment of NP-specific cytotoxic CD8 T cells was observed in the lungs of SAM(NP)-immunized mice after influenza infection that paralleled with reduced lung viral titers and pathology, and increased survival after homologous and heterosubtypic influenza challenge. Finally, we demonstrated for the first time that the co-administration of RNA (SAM(M1-NP)) and protein (monovalent inactivated influenza vaccine (MIIV)) was feasible, induced simultaneously NP-, M1- and HA-specific T cells and HA-specific neutralizing antibodies, and enhanced MIIV efficacy against a heterologous challenge. In conclusion, systemic administration of SAM vectors expressing conserved internal influenza antigens induced protective immune responses in mice, supporting the SAM® platform as another promising strategy for the development of broad-spectrum universal influenza vaccines.

Indexed as

Conserved SequenceAnimalsAntigens, ViralCell LineCricetinaeGene AmplificationGene ExpressionGenetic VectorsInfluenza A virusInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H3N2 SubtypeInfluenza VaccinesLungMiceRNA, MessengerT-Lymphocytes, CytotoxicAntigens, ViralInfluenza VaccinesM1 protein, Influenza A virusRNA, MessengerVaccines, InactivatedViral Core ProteinsViral Matrix Proteins

Identifiers

PMID27525409
PMCPMC4985159
OpenAlexW2515313544

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.