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

Kautilya K Jena1,2, Pengxiang Qu3, Lauren Baracco4

  • 1Harvard Medical School, Boston, MA, USA.

Nature Immunology
|May 22, 2026
PubMed

Insights

Combining mRNA vaccines with mannadjuvant, a fungal mannan formulation, boosts immune responses against SARS-CoV-2 variants. This approach enhances vaccine efficacy and durability by tuning inflammation via pattern recognition receptor (PRR) stimulation.

Area of Science:

  • Immunology
  • Vaccinology
  • Microbiology

Background:

  • Pattern recognition receptors (PRRs) play a crucial role in orchestrating inflammation and regulating adaptive immunity.
  • mRNA vaccines have shown promise but can be further enhanced for broader and more durable protection.

Purpose of the Study:

  • To investigate whether modulating inflammation through PRR stimulation can improve the efficacy of mRNA vaccines.
  • To evaluate the combination of an mRNA vaccine against SARS-CoV-2 with mannadjuvant, a dectin-2 targeting formulation.

Main Methods:

  • Developed an mRNA vaccine targeting the ancestral SARS-CoV-2 spike protein.
  • Combined the mRNA vaccine with mannadjuvant (fungal mannan and aluminum hydroxide) for PRR dectin-2 stimulation.
  • Assessed immune responses in mice and non-human primates, including antibody neutralization and cytokine production.

Main Results:

  • Mannadjuvant significantly increased the magnitude and durability of the immune response elicited by the mRNA vaccine.
  • The combination therapy induced neutralizing antibodies effective against SARS-CoV-2 variants with high escape potential, overcoming antigenic imprinting.
  • Mechanistic studies revealed that prolonged type I interferon (IFN) production and enhanced interleukin-1 (IL-1) signaling were critical for mannadjuvant's effects.

Conclusions:

  • Antifungal PRRs can be effectively harnessed to enhance mRNA vaccine potency and durability.
  • The combination of mRNA vaccines with mannadjuvant represents a promising strategy for developing next-generation vaccines against viral threats.
  • Targeting PRRs offers a novel approach to overcome challenges like antigenic imprinting and variant escape in vaccine development.

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