{
  "abstract": "Rapid development of host immunity is critical during the emergence of viral outbreaks when vaccines are not yet available. Here, we demonstrate that CpG oligodeoxynucleotide-schizophyllan complex (K3-SPG) induces antigen-independent, long-term protection against lethal respiratory virus infection. A single intranasal administration successfully enhanced host resistance to infection for as long as 100 days posttreatment. Mechanistically, we observed a lung-restricted biphasic innate activation of macrophages and innate lymphoid cells. Early protection was mediated by CD11b + CD11c + macrophages (DP MΦ) and monocyte-derived interstitial macrophages (IMΦ). Late protection was mediated by innate lymphoid cells that were epigenetically reprogrammed, suggesting that two distinct innate immune subsets contribute to the maintenance of disease tolerance in the lung microenvironment. Deficiency of TLR9 or TNF-α abrogated innate activation and protective immunity. Collectively, these findings demonstrate that adjuvant-induced prophylaxis is a promising approach to enhancing host resistance against respiratory virus infection, involving the biphasic cooperation between innate immune cells in the local tissue.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.",
    "Department of Computational Biology and Medical Science, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.",
    "International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.",
    "Division of Rheumatology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.",
    "Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Japan.",
    "Leprosy Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.",
    "Division of Malaria Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.",
    "The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), University of Tokyo, Tokyo, Japan.",
    "Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.",
    "Department of Immunology, Hyogo Medical University School of Medicine, Nishinomiya, Hyogo, Japan.",
    "Institute for Vaccine Research and Development, Hokkaido University, Sapporo, Hokkaido, Japan."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Asuka Joy Tobuse",
      "orcid": "0000-0002-2617-7651"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Kouji Kobiyama",
      "orcid": "0000-0002-5846-4807"
    },
    {
      "affs": [
        0
      ],
      "name": "Jun Tsuchida"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Masamitsu N. Asaka"
    },
    {
      "affs": [
        4
      ],
      "name": "Daichi Utsumi",
      "orcid": "0000-0001-6602-8426"
    },
    {
      "affs": [
        2,
        6,
        7
      ],
      "name": "Mariana Silva Almeida",
      "orcid": "0000-0001-9694-3721"
    },
    {
      "affs": [
        8
      ],
      "name": "Yaeko Nakajima-Takagi",
      "orcid": "0000-0002-2341-2409"
    },
    {
      "affs": [
        8
      ],
      "name": "Motohiko Oshima",
      "orcid": "0000-0001-6991-815X"
    },
    {
      "affs": [
        0,
        2,
        7
      ],
      "name": "Tomoya Hayashi",
      "orcid": "0000-0003-3189-6463"
    },
    {
      "affs": [
        0,
        2,
        7
      ],
      "name": "Burcu Temizoz",
      "orcid": "0000-0002-5189-3529"
    },
    {
      "affs": [
        9
      ],
      "name": "Etsushi Kuroda",
      "orcid": "0000-0002-7198-2190"
    },
    {
      "affs": [
        1,
        2,
        6,
        7
      ],
      "name": "Cevayir Coban",
      "orcid": "0000-0002-4467-7799"
    },
    {
      "affs": [
        4,
        10
      ],
      "name": "Yasuhiro Yasutomi",
      "orcid": "0000-0001-8252-1448"
    },
    {
      "affs": [
        1,
        7,
        8
      ],
      "name": "Atsushi Iwama",
      "orcid": "0000-0001-9410-8992"
    },
    {
      "affs": [
        0,
        1,
        2,
        7
      ],
      "name": "Ken J. Ishii",
      "orcid": "0000-0002-6728-3872"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ccr9ceywex189.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aeh6480",
  "fulltext_url": null,
  "id": "ccr9ceywex189",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aeh6480",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Immune Response and Inflammation"
    ]
  ],
  "openalex": "W7221092283",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/ccr9ceywex189.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aeh6480",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aeh6480"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune Response and Inflammation",
      "subfield": "immunology"
    }
  ],
  "title": "Long-term immunoprophylaxis by TLR9 ligand mediates macrophage-ILC cross-talk against respiratory viral infection",
  "title_text": "Long-term immunoprophylaxis by TLR9 ligand mediates macrophage-ILC cross-talk against respiratory viral infection",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:41Z",
  "url": "https://research.draconitic.com/paper/ccr9ceywex189",
  "venue": "Science Advances",
  "versions": []
}