Evidence map›Paper›PMID 33535570›Full record

ArticlePharmaceutics2021

Cyclic Di-Adenosine Monophosphate: A Promising Adjuvant Candidate for the Development of Neonatal Vaccines.

Darío Lirussi, Sebastian Felix Weissmann, Thomas Ebensen, Ursula Nitsche-Gloy, Heiko B G Franz, Carlos A Guzmán

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

8 citing papers in PubMed, 13 citations in OpenAlex.

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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

6 authors at 2 institutions in 1 country.

Darío LirussiDepartment of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.ORCID 0000-0002-3054-2586
Sebastian Felix WeissmannDepartment of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Thomas EbensenDepartment of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Ursula Nitsche-GloyWomen's Clinic, Hospital Marienstift GmbH, Helmstedter Strasse 35, 38102 Braunschweig, Germany.
Heiko B G FranzDepartment of Obstetrics and Gynecology, Women's Clinic, Braunschweig Central Hospital, Celler Strasse 38, 38114 Braunschweig, Germany.
Carlos A GuzmánDepartment of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Helmholtz Centre for Infection Research · DEKlinikum Braunschweig · DE

Funding

EC Horizon 2020 730964 (TransVac2)European Community's Seventh Framework Program 601738 (Univax)Helmholtz Association HAI-IDR
6 · The paper itself

Abstract

Underdeveloped immunity during the neonatal age makes this period one of the most dangerous during the human lifespan, with infection-related mortality being one of the highest of all age groups. It is also discussed that vaccination during this time window may result in tolerance rather than in productive immunity, thus raising concerns about the overall vaccine-mediated protective efficacy. Cyclic di-nucleotides (CDN) are bacterial second messengers that are rapidly sensed by the immune system as a danger signal, allowing the utilization of these molecules as potent activators of the immune response. We have previously shown that cyclic di-adenosine monophosphate (CDA) is a potent and versatile adjuvant capable of promoting humoral and cellular immunity. We characterize here the cytokine profiles elicited by CDA in neonatal cord blood in comparison with other promising neonatal adjuvants, such as the imidazoquinoline resiquimod (R848), which is a synthetic dual TLR7 and TLR8 agonist. We observed superior activity of CDA in eliciting T helper 1 (Th1) and T follicular helper (TfH) cytokines in cells from human cord blood when compared to R848. Additional in vivo studies in mice showed that neonatal priming in a three-dose vaccination schedule is beneficial when CDA is used as a vaccine adjuvant. Humoral antibody titers were significantly higher in mice that received a neonatal prime as compared to those that did not. This effect was absent when using other adjuvants that were reported as suitable for neonatal vaccination. The biological significance of this immune response was assessed by a challenge with a genetically modified influenza H1N1 PR8 virus. The obtained results confirmed that CDA performed better than any other adjuvant tested. Altogether, our results suggest that CDA is a potent adjuvant in vitro on human cord blood, and in vivo in newborn mice, and thus a suitable candidate for the development of neonatal vaccines.

Indexed as

cyclic di-adenosine monophosphate (CDA)cyclic di-nucleotides (CDN)first dose efficacyneonatal vaccinesstimulator of interferon genes (STING)

Identifiers

PMID33535570
PMCPMC7912751
OpenAlexW3127568978

What OpenQuestion holds

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Registered trials

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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.