Evidence map›Paper›PMID 40231823›Full record

ArticleJournal of virology2025

ARNAX is an ideal adjuvant for COVID-19 vaccines to enhance antigen-specific CD4

Tomomi Kawakita, Toshiki Sekiya, Yayoi Kameda, Naoki Nomura, Marumi Ohno, Chimuka Handabile, Akari Yamaya, Hideo Fukuhara, Yuki Anraku, Shunsuke Kita and 15 more

Abstract read
In one paragraph

Article in Journal of virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Immunomodulatory effects of probioticFrontiers in microbiology · 2025
    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

25 authors.

Tomomi KawakitaDivision of Vaccine Immunology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.ORCID 0000-0003-3723-0013
Toshiki SekiyaInstitute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan.
Yayoi KamedaDivision of Bioresources, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Naoki NomuraDivision of Biologics Development, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Marumi OhnoInstitute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan.ORCID 0000-0003-1086-8244
Chimuka HandabileInstitute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan.
Akari YamayaNebuta Research Institute for Life Sciences, Aomori University, Aomori, Japan.
Hideo FukuharaInstitute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan.
Yuki AnrakuLaboratory of Biomolecular Science, and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.ORCID 0000-0002-5731-0902
Shunsuke KitaInstitute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan.
Shinsuke TobaShionogi Pharmaceutical Research Center, Shionogi & Company, Limited, Toyonaka, Japan.
Hirotake TsukamotoDivision of Clinical Immunology and Cancer Immunotherapy, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tomohiro SawaDepartment of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Hiroyuki OshiumiDepartment of Immunology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Yasushi ItohDivision of Pathogenesis and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.ORCID 0000-0001-7462-2193
Katsumi MaenakaInstitute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan.
Akihiko SatoInstitute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan.ORCID 0000-0001-6625-1679
Hirofumi SawaInstitute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan.
Yasuhiko SuzukiInstitute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan.ORCID 0000-0002-1313-1494
Lorena E BrownInternational Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.ORCID 0000-0001-9342-909X
David C JacksonInternational Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Hiroshi KidaDivision of Vaccine Immunology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.ORCID 0000-0003-4876-1004
Misako MatsumotoDivision of Vaccine Immunology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Tsukasa SeyaDivision of Vaccine Immunology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.ORCID 0000-0002-0808-5710
Masashi ShingaiDivision of Vaccine Immunology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.ORCID 0000-0003-3214-4626

Funding

Japan Agency for Medical Research and Development 22fk0108142Japan Agency for Medical Research and Development 23gm1610011Japan Agency for Medical Research and Development JP17am0101093Japan Agency for Medical Research and Development JP19fm0108008Japan Agency for Medical Research and Development JP20ae0101047Japan Agency for Medical Research and Development JP21fk0108463Japan Agency for Medical Research and Development JP22ama121037Japan Agency for Medical Research and Development JP243fa627005Japan Agency for Medical Research and Development JP243fa627008Japan Agency for Medical Research and Development JP243fa827012Japan Agency for Medical Research and Development JP243fa827021Japan Agency for Medical Research and Development JP24wm0125008Japan Society for the Promotion of Science 21H02376Japan Society for the Promotion of Science 22K15483Japan Society for the Promotion of Science 23K15362Japan Society for the Promotion of Science JP20H05873
6 · The paper itself

Abstract

ARNAX is a synthetic nucleotide-based Toll-like receptor 3 (TLR3) ligand that specifically stimulates the TLR3/TIR domain-containing adaptor molecule 1 (TICAM-1) pathway without activating inflammatory responses. ARNAX activates cellular immunity via cross-presentation; hence, its practical application has been demonstrated in cancer immunotherapy. Given the importance of cellular immunity in virus infections, ARNAX is expected to be a more effective vaccine adjuvant for virus infections than alum, an adjuvant approved for human use that mainly enhances humoral immunity. In the present study, the trimeric recombinant spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was prepared as a vaccine antigen and formulated with ARNAX. When T-cell and neutralizing antibody responses were evaluated in immunized mice, antigen formulated with ARNAX generated significantly larger numbers of antigenspecific CD4 IMPORTANCE: Cellular immunity is a critical immunological defense system against virus infections. However, aluminum salts, the most widely used adjuvant for vaccines for human use, do not promote strong cellular immunity. To prepare for the next pandemic of viral origin, the development of Th1-type adjuvants with low adverse reactions that induce cellular immunity is necessary. ARNAX is a TLR3 agonist consisting of DNA-RNA hybrid nucleic acid, which is expected to be an adjuvant that induces cellular immunity. The present study using a coronavirus disease 2019 mouse model demonstrated that ARNAX potently induces cellular immunity in addition to humoral immunity with minimal induction of inflammatory cytokines. Therefore, ARNAX has the potential to be used as a potent and welltolerated adjuvant for vaccines against pandemic viruses emerging in the future.

Indexed as

Adjuvants, ImmunologicAdjuvants, VaccineAntibodies, NeutralizingCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCOVID-19COVID-19 VaccinesSARS-CoV-2AnimalsAntibodies, ViralFemaleHumansImmunity, CellularMiceMice, Inbred BALB CSpike Glycoprotein, CoronavirusAdjuvants, ImmunologicAdjuvants, VaccineAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2adjuvantARNAXCOVID-19TLR3

Identifiers

PMID40231823
PMCPMC12090777

What OpenQuestion holds

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LicenceCC BY
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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.