Evidence map›Paper›PMID 39749328›Full record

ArticleFrontiers in immunology2024

MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity.

Ilka Grewe, Monika Friedrich, Marie-Louise Dieck, Michael Spohn, My Linh Ly, Verena Krähling, Leonie Mayer, Sibylle C Mellinghoff, Monika Rottstegge, Rebekka Kraemer and 6 more

2 registry-linked trialsAbstract readClinical Trial, Phase I
In one paragraph

Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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.

NCT04569383 phase1completednot on this map

An Open, Single-center Phase I Trial to Assess the Safety, Tolerability and Immunogenicity of Two Ascending Doses of the Candidate Vaccine MVA-SARS-2-S and Heterologous Booster Vaccinations With a Licensed Vaccine Against COVID-19

TypeinterventionalSponsorUniversitätsklinikum Hamburg-EppendorfRan2020 to 2021Enrolled30ConditionsCovid19ArmsMVA-SARS-2-S vaccinations (days 0 & 28), Comirnaty
NCT04895449 phase1completednot on this map

A Multi-center Phase Ib Trial to Assess the Safety, Tolerability and Immunogenicity of the Candidate Vaccine MVA-SARS-2-ST in Adults

TypeinterventionalSponsorUniversitätsklinikum Hamburg-EppendorfRan2021 to 2022Enrolled43ConditionsCovid19ArmsMVA-SARS-2-ST
3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
  4. Article
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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

16 authors.

Ilka GreweInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Monika FriedrichInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Marie-Louise DieckInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Michael SpohnResearch Institute Children's Cancer Center Hamburg, Hamburg, Germany.
My Linh LyInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Verena KrählingInstitute of Virology, Philipps University Marburg, Marburg, Germany.
Leonie MayerInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Sibylle C MellinghoffInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Monika RottsteggeInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Rebekka KraemerInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Medical Center Schleswig-Holstein, Kiel, Germany.
Asisa VolzInstitute of Virology, University of Veterinary Medicine Hannover, Hanover, Germany.
Stephan BeckerInstitute of Virology, Philipps University Marburg, Marburg, Germany.
Anahita FathiInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Christine DahlkeInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Leonie M Weskamm *Institute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Marylyn M Addo *Institute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Vaccine platforms such as viral vectors and mRNA can accelerate vaccine development in response to newly emerging pathogens, as demonstrated during the COVID-19 pandemic. However, the differential effects of platform and antigen insert on vaccine immunogenicity remain incompletely understood. Innate immune responses induced by viral vector vaccines are suggested to have an adjuvant effect for subsequent adaptive immunity. Integrating data on both innate and adaptive immunity, systems vaccinology approaches can improve the understanding of vaccine-induced immune mechanisms. Methods: Two vaccine candidates against SARS-CoV-2, both based on the viral vector Modified Vaccinia virus Ankara (MVA) and encoding the native (MVA-SARS-2-S) or prefusion-stabilized spike protein (MVA-SARS-2-ST), were evaluated in phase 1 clinical trials (ClinicalTrials.gov: NCT04569383, NCT04895449). Longitudinal dynamics of innate and early adaptive immune responses induced by vaccination in SARS-CoV-2-naïve individuals were analyzed based on transcriptome and flow cytometry data, in comparison to the licensed ChAd and mRNA vaccines. Results: Compared to MVA-SARS-2-S, MVA-SARS-2-ST (encoding the prefusion-stabilized spike protein) induced a stronger transcriptional activation early after vaccination, as well as higher virus neutralizing antibodies. Positive correlations were observed between innate and adaptive immune responses induced by a second MVA-SARS-2-ST vaccination. MVA-, ChAd- and mRNA-based vaccines induced distinct immune signatures, with the overall strongest transcriptional activation as well as monocyte and circulating T follicular helper (cTFH) cell responses induced by ChAd. Discussion: Our findings suggest a potential impact of the spike protein conformation not only on adaptive but also on innate immune responses. As indicated by positive correlations between several immune parameters induced by MVA-SARS-2-ST, the distinct transcriptional activation early after vaccination may be linked to the induction of classical monocytes and activation of cTFH1 cells, which may in turn result in the superior adaptive immunogenicity of MVA-SARS-2-ST, compared to MVA-SARS-2-S. Overall, our data demonstrate that both the vaccine platform and antigen insert can affect innate immune responses and subsequent vaccine immunogenicity in humans.

Indexed as

Adaptive ImmunityCOVID-19COVID-19 VaccinesSARS-CoV-2Spike Glycoprotein, CoronavirusAdultAntibodies, NeutralizingAntibodies, ViralFemaleHumansImmunity, InnateImmunogenicity, VaccineMaleMiddle AgedVaccinationVaccines, DNAAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Vaccines, DNACOVID-19innate immunitymodified vaccinia virus AnkaraSARS-CoV-2spike proteinsystems vaccinologyT follicular helper cellstranscriptome

Identifiers

PMID39749328
PMCPMC11693667

What Socratic holds

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LicenceCC BY
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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 Socratic graph.