A glycan-based adjuvant expands the breadth and duration of protection of mRNA-based vaccines

Kautilya K. Jena; Pengxiang Qu; Lauren Baracco; Shahab Saghaei; Keerti; Zahra Allahyari; Daniel Boehmer; Moriah Mitchell; Carly A. Dillen; Hai Yun Li; Enqi Liu; Valentina Poli; Océane Dufies; David P. Hoytema van Konijnenburg; Roberto Spreafico; Caihong Bi; Rebecca Hall; Michael D. Kruppa; Zuchao Ma; Amy Gravitte; Douglas W. Lowman; Harry E. Ensley; Pierre Marty; Laurent Boyer; Rémy Collomp; David L. Williams; Victor Pui Yan Ma; Pui Y. Lee; Peter A. Nigrovic; Jeffrey M. Karp; Stephen J. Elledge; Duane R. Wesemann; Yi Wu; Matthew Frieman; Ivan Zanoni

doi:10.1038/s41590-026-02517-3

A glycan-based adjuvant expands the breadth and duration of protection of mRNA-based vaccines

Kautilya K. Jena
, Pengxiang Qu
, Lauren Baracco
, Shahab Saghaei
, Keerti
, Zahra Allahyari
, Daniel Boehmer
, Moriah Mitchell
, Carly A. Dillen
, Hai Yun Li
, Enqi Liu
, Valentina Poli
, Océane Dufies
, David P. Hoytema van Konijnenburg
, Roberto Spreafico
, Caihong Bi
, Rebecca Hall
, Michael D. Kruppa
, Zuchao Ma
, Amy Gravitte

Douglas W. Lowman, Harry E. Ensley, Pierre Marty, Laurent Boyer, Rémy Collomp, David L. Williams, Victor Pui Yan Ma, Pui Y. Lee, Peter A. Nigrovic, Jeffrey M. Karp, Stephen J. Elledge, Duane R. Wesemann, Yi Wu, Matthew Frieman, Ivan Zanoni

Harvard University
Boston Children's Hospital
Xi'an Jiaotong University
University of Maryland, Baltimore
Brigham and Women’s Hospital
Massachusetts Institute of Technology
The Second Affiliated Hospital of Xi'an Jiaotong University
University of California at Los Angeles
East Tennessee State University
Centre Méditerranéen de Médecine Moléculaire
CHU de Nice
Harvard-Massachusetts Institutes of Technology Health Sciences and Technology
Broad Institute

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Journal	Nature Immunology
DOIs	https://doi.org/10.1038/s41590-026-02517-3
State	Accepted/In press - 2026
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/s41590-026-02517-3

Cite this

Jena, K. K., Qu, P., Baracco, L., Saghaei, S., Keerti, Allahyari, Z., Boehmer, D., Mitchell, M., Dillen, C. A., Li, H. Y., Liu, E., Poli, V., Dufies, O., Hoytema van Konijnenburg, D. P., Spreafico, R., Bi, C., Hall, R., Kruppa, M. D., Ma, Z., ... Zanoni, I. (Accepted/In press). A glycan-based adjuvant expands the breadth and duration of protection of mRNA-based vaccines. Nature Immunology. https://doi.org/10.1038/s41590-026-02517-3

@article{5d5616e28ba84534b44afa41fe2d4e2e,

title = "A glycan-based adjuvant expands the breadth and duration of protection of mRNA-based vaccines",

abstract = "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.",

author = "Jena, \{Kautilya K.\} and Pengxiang Qu and Lauren Baracco and Shahab Saghaei and Keerti and Zahra Allahyari and Daniel Boehmer and Moriah Mitchell and Dillen, \{Carly A.\} and Li, \{Hai Yun\} and Enqi Liu and Valentina Poli and Oc{\'e}ane Dufies and \{Hoytema van Konijnenburg\}, \{David P.\} and Roberto Spreafico and Caihong Bi and Rebecca Hall and Kruppa, \{Michael D.\} and Zuchao Ma and Amy Gravitte and Lowman, \{Douglas W.\} and Ensley, \{Harry E.\} and Pierre Marty and Laurent Boyer and R{\'e}my Collomp and Williams, \{David L.\} and Ma, \{Victor Pui Yan\} and Lee, \{Pui Y.\} and Nigrovic, \{Peter A.\} and Karp, \{Jeffrey M.\} and Elledge, \{Stephen J.\} and Wesemann, \{Duane R.\} and Yi Wu and Matthew Frieman and Ivan Zanoni",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2026.",

year = "2026",

doi = "10.1038/s41590-026-02517-3",

language = "英语",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Research",

}

Jena, KK, Qu, P, Baracco, L, Saghaei, S, Keerti, Allahyari, Z, Boehmer, D, Mitchell, M, Dillen, CA, Li, HY, Liu, E, Poli, V, Dufies, O, Hoytema van Konijnenburg, DP, Spreafico, R, Bi, C, Hall, R, Kruppa, MD, Ma, Z, Gravitte, A, Lowman, DW, Ensley, HE, Marty, P, Boyer, L, Collomp, R, Williams, DL, Ma, VPY, Lee, PY, Nigrovic, PA, Karp, JM, Elledge, SJ, Wesemann, DR, Wu, Y, Frieman, M & Zanoni, I 2026, 'A glycan-based adjuvant expands the breadth and duration of protection of mRNA-based vaccines', Nature Immunology. https://doi.org/10.1038/s41590-026-02517-3

TY - JOUR

T1 - A glycan-based adjuvant expands the breadth and duration of protection of mRNA-based vaccines

AU - Jena, Kautilya K.

AU - Qu, Pengxiang

AU - Baracco, Lauren

AU - Saghaei, Shahab

AU - Keerti,

AU - Allahyari, Zahra

AU - Boehmer, Daniel

AU - Mitchell, Moriah

AU - Dillen, Carly A.

AU - Li, Hai Yun

AU - Liu, Enqi

AU - Poli, Valentina

AU - Dufies, Océane

AU - Hoytema van Konijnenburg, David P.

AU - Spreafico, Roberto

AU - Bi, Caihong

AU - Hall, Rebecca

AU - Kruppa, Michael D.

AU - Ma, Zuchao

AU - Gravitte, Amy

AU - Lowman, Douglas W.

AU - Ensley, Harry E.

AU - Marty, Pierre

AU - Boyer, Laurent

AU - Collomp, Rémy

AU - Williams, David L.

AU - Ma, Victor Pui Yan

AU - Lee, Pui Y.

AU - Nigrovic, Peter A.

AU - Karp, Jeffrey M.

AU - Elledge, Stephen J.

AU - Wesemann, Duane R.

AU - Wu, Yi

AU - Frieman, Matthew

AU - Zanoni, Ivan

PY - 2026

Y1 - 2026

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105039908558

U2 - 10.1038/s41590-026-02517-3

DO - 10.1038/s41590-026-02517-3

M3 - 文章

AN - SCOPUS:105039908558

SN - 1529-2908

JO - Nature Immunology

JF - Nature Immunology

ER -

A glycan-based adjuvant expands the breadth and duration of protection of mRNA-based vaccines

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