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Synthesis and Characterization of mRNA-Loaded Poly(Beta Aminoesters) Nanoparticles for Vaccination Purposes
Published on: August 13, 2021
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.
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.
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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