A glycan-based adjuvant expands the breadth and duration of protection of mRNA-based vaccines PMID: 42174265

ADC Targets in Oncology

2026-04-10

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

Nat Immunol. 2026 Jun;27(6):1130-1144. doi: 10.1038/s41590-026-02517-3.

Kautilya K Jena ^# ¹ ² , Pengxiang Qu ^# ³ , Lauren Baracco ⁴ , Shahab Saghaei ¹ ⁵ ⁶ , Keerti ¹ ⁵ ⁶ , Zahra Allahyari ¹ ⁵ ⁶ , Daniel Boehmer ¹ ² , Moriah Mitchell ¹ ⁷ , Carly A Dillen ⁴ , Hai-Yun Li ⁸ , Enqi Liu ³ , Valentina Poli ¹ ² , Océane Dufies ¹ ² , David P Hoytema van Konijnenburg ¹ ² , Roberto Spreafico ⁹ , Caihong Bi ¹ ⁵ ⁶ , Rebecca Hall ¹ ² , Michael D Kruppa ¹⁰ , Zuchao Ma ¹⁰ , Amy Gravitte ¹⁰ , Douglas W Lowman ¹⁰ , Harry E Ensley ¹⁰ , Pierre Marty ¹¹ , Laurent Boyer ¹¹ , Rémy Collomp ¹² , David L Williams ¹⁰ , Victor Pui-Yan Ma ¹ ¹³ ¹⁴ ¹⁵ ¹⁶ , Pui Y Lee ¹ ² , Peter A Nigrovic ¹ ² , Jeffrey M Karp ¹ ¹³ ¹⁴ ¹⁵ ¹⁶ , Stephen J Elledge ¹ ⁷ , Duane R Wesemann ¹ ⁵ ⁶ , Yi Wu ¹⁷ , Matthew Frieman ⁴ , Ivan Zanoni ¹⁸ ¹⁹ ²⁰

Affiliations

1. Harvard Medical School, Boston, MA, USA.
2. Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
3. Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, China.
4. University of Maryland School of Medicine, Department of Microbiology and Immunology, Baltimore, MD, USA.
5. Division of Allergy and Clinical Immunology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
6. Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
7. Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Boston, MA, USA.
8. Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, Laboratory Animal Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.
9. Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
10. Department of Biomedical Sciences and Department of Surgery, Quillen College of Medicine, Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, TN, USA.
11. Université Côte d'Azur, Inserm, C3M, and Parasitologie-Mycologie CHU de Nice, Nice, France.
12. Pôle Pharmacie, CHU de Nice, Nice, France.
13. Center for Nanomedicine, Department Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard-MIT Division of Health Sciences and Technology, Boston, MA, USA.
14. Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
15. Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
16. Broad Institute of MIT & Harvard, Cambridge, MA, USA.
17. Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, Laboratory Animal Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China. [email protected].
18. Harvard Medical School, Boston, MA, USA. [email protected].
19. Boston Children's Hospital, Division of Immunology, Boston, MA, USA. [email protected].
20. Boston Children's Hospital, Division of Gastroenterology, Boston, MA, USA. [email protected].
# Contributed equally.

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.