A glycan-based adjuvant expands the breadth and duration of protection of mRNA-based vaccines
The activation of pattern recognition receptors (PRRs) orchestrates inflammation and regulates adaptive immunity. To test whether tuning inflammation through PRR stimulation enhanced the efficacy of mRNA vaccines, we combined an mRNA-based vaccine generated against the ancestral spike protein of SARS-CoV-2 with mannadjuvant, a formulation of fungal mannan and aluminum hydroxide targeting the PRR dectin-2. In mice and non-human primates, mannadjuvant increased the magnitude and durability of the response elicited by the mRNA-based vaccine, and it also led to the induction of neutralizing antibodies directed against variants of concern with a high escape capacity, overcoming antigenic imprinting. Mechanistically, prolonged type I interferon (IFN) production and potentiated interleukin-1 (IL-1) signaling locally within the draining lymph node in mice or in human cells were necessary and sufficient to exert the effect of mannadjuvant. Our data indicate that antifungal PRRs can be harnessed to create more potent and durable mRNA-based vaccines. Jena, Qu et al. show that mannadjuvant, a formulation of fungal mannan and aluminum hydroxide, increases the magnitude, durability and breadth of the response elicited by mRNA-based vaccines against SARS-CoV-2 variants in mice and non-human primates.
Authors
- Enqi Liu (ORCID: https://orcid.org/0000-0002-2092-3158)
- David P. Hoytema van Konijnenburg (ORCID: https://orcid.org/0000-0001-5198-9718)
- Jeffrey M. Karp (ORCID: https://orcid.org/0000-0002-4752-7374)
- Victor Pui‐Yan (ORCID: https://orcid.org/0000-0002-5951-0297)
- Stephen J. Elledge (ORCID: https://orcid.org/0000-0001-7923-6283)
- Harry E. Ensley
- Rémy Collomp
- Rebecca Hall
- Daniël Boehmer
- Ivan Zanoni (ORCID: https://orcid.org/0000-0002-3423-7474)
- Haiyun Li (ORCID: https://orcid.org/0000-0002-7458-7399)
- Caihong Bi (ORCID: https://orcid.org/0009-0001-2570-7542)
- Zahra Allahyari (ORCID: https://orcid.org/0000-0002-8274-9538)
- Zuchao Ma (ORCID: https://orcid.org/0000-0001-6363-835X)
- Pengxiang Qu (ORCID: https://orcid.org/0000-0001-7858-9124)
- Valentina Poli (ORCID: https://orcid.org/0000-0001-8637-8204)
- Océane Dufies (ORCID: https://orcid.org/0000-0001-7076-969X)
- Lauren Baracco (ORCID: https://orcid.org/0000-0002-6984-5832)
- Roberto Spreafico (ORCID: https://orcid.org/0000-0001-8282-7658)
- Carly Dillen (ORCID: https://orcid.org/0000-0001-5227-5952)
- Michael D. Kruppa (ORCID: https://orcid.org/0000-0002-1747-2333)
- Douglas W. Lowman (ORCID: https://orcid.org/0000-0002-2080-3447)
- Peter A. Nigrovic
- Shahab Saghaei
- Pierre Marty (ORCID: https://orcid.org/0000-0002-0231-3751)
- Matthew Frieman
- Duane R. Wesemann
- Amy Gravitte
- Pui Y. Lee (ORCID: https://orcid.org/0000-0002-5779-4193)
- Moriah Mitchell
- Yi Wu (ORCID: https://orcid.org/0000-0003-0365-5590)
- Laurent Boyer (ORCID: https://orcid.org/0000-0002-1375-1706)
- Keerti
- Kautilya K. Jena (ORCID: https://orcid.org/0000-0002-7568-1555)
- David L. Williams
Institutions
- QB3 (US)
- Broad Institute (US)
- East Tennessee State University (US)
- University of Maryland, Baltimore (US)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Inserm (FR)
- University of California, Los Angeles (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- Centre Hospitalier Universitaire de Nice (FR)
- Harvard–MIT Division of Health Sciences and Technology (US)
- Second Affiliated Hospital of Xi'an Jiaotong University (CN)
- Boston Children's Museum (US)
- Harvard Stem Cell Institute (US)
- Xi'an Jiaotong University (CN)
Publication Details
- Journal
- Nature Immunology
- Published
- 2026-05-22
- DOI
- https://doi.org/10.1038/s41590-026-02517-3
- Primary Topic
- Immune responses and vaccinations
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institute of Allergy and Infectious Diseases