Evidence map›Paper›PMID 40617088›Full record

ArticleVaccine2025

Self-amplifying mRNA expressing COBRA hemagglutinin elicits long-lasting, broadly reactive antibodies against seasonal influenza A viruses.

Spencer R Pierce, Hua Shi, Camila Caetano, David A Prots, Michael A Carlock, Audrey M Cervantes, Brian L Hua, Amy R Rappaport, Heather Larson, Ciaran D Scallan and 2 more

Abstract read
In one paragraph

Article in Vaccine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

12 authors.

Spencer R PierceCenter for Vaccines and Immunology, University of Georgia, Athens, GA, USA; Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL, USA.
Hua ShiCenter for Vaccines and Immunology, University of Georgia, Athens, GA, USA.
Camila CaetanoLehner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
David A ProtsLehner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Michael A CarlockCenter for Vaccines and Immunology, University of Georgia, Athens, GA, USA; Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL, USA.
Audrey M CervantesGritstone Bio, Emeryville, CA, USA.
Brian L HuaGritstone Bio, Emeryville, CA, USA.
Amy R RappaportGritstone Bio, Emeryville, CA, USA.
Heather LarsonGritstone Bio, Emeryville, CA, USA.
Ciaran D ScallanGritstone Bio, Emeryville, CA, USA.
Karin JoossGritstone Bio, Emeryville, CA, USA.
Ted M RossCenter for Vaccines and Immunology, University of Georgia, Athens, GA, USA; Department of Infectious Diseases, University of Georgia, Athens, GA, USA; Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL, USA; Lehner Research Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: rosst7@ccf.org.

Funding

COVID Supplement - COMPONENT A OF THE COLLABORATIVE INFLUENZA VACCINE INNOVATION CENTERS (CIVICS) PROGRAM TO DESIGN AND EVALUATE INNOVATIVE INFLUENZA VACCINE APPROACHES,75N93019C00052 · NIAID · UNIVERSITY OF GEORGIA · PI ROSS, TED · 2019 to 2025
$74.6M
NIAID NIH HHS 75N93019C00052
6 · The paper itself

Abstract

Development of universal or broadly-reactive influenza virus vaccines is critical for addressing emerging pandemic strains, as well as improving the effectiveness and longevity of annual, seasonal influenza virus vaccines. The next generation of influenza vaccines need to address expanding the breadth of vaccine induced immune response to neutralize drifted variants, enhance the longevity of elicited immunity, and preferably use single-shot platforms that will reduce the number of vaccinations and expand the number of doses available. In this report, influenza hemagglutinin sequences, developed using computationally optimized broadly-reactive antigen (COBRA) methodology, were expressed from a self-amplifying mRNA (samRNA) vector to elicit broadly-reactive, protective immunity following a single vaccination of mice or ferrets. Three COBRA HA antigens representing an H1 HA (Y2) or two H3 HA (J4 or NG2) were expressed from individual samRNA vectors and administered individually or mixed as H1/H3 HA samRNA vaccines. In addition, two HA antigens were expressed from the same vector (Y2-J4 or Y2-NG2) as a dual expressing samRNA vaccine. Mice or ferrets vaccinated with these samRNA vaccines had long-lasting antibodies with hemagglutination-inhibition activity against a panel of H1N1 and H3N2 influenza strains representing past, current, and future drifted influenza virus variants. In addition, samRNA expressed COBRA HA antigens elicited H1 and H3 specific T cell resposnes against HA head and stem regions. Animals challenged with H1N1 or H3N2 influenza viruses had little weight loss or signs of morbidity and little to no virus detected in the lungs or nasal washes following challenge. Overall, samRNA vectors, expressing COBRA HA antigens, efficiency elicited broadly-reactive and protective immune responses following a single vaccination.

Indexed as

Antibodies, ViralHemagglutinin Glycoproteins, Influenza VirusInfluenza A virusInfluenza VaccinesRNA, MessengerAnimalsFemaleFerretsInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H3N2 SubtypeMiceMice, Inbred BALB COrthomyxoviridae InfectionsVaccinationVaccines, SyntheticAntibodies, ViralHemagglutinin Glycoproteins, Influenza VirusInfluenza VaccinesRNA, MessengerVaccines, SyntheticFerretsHemagglutininInfluenzaMicesamRNAVaccine

Identifiers

PMID40617088
PMCPMC12302018

What OpenQuestion holds

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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.