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Tailoring mRNA lipid nanoparticles for antifungal vaccines

Summary

Researchers are exploring mRNA vaccines, similar to those used for COVID-19, as a new approach to prevent fungal infections. These vaccines use fatty particles called lipid nanoparticles to deliver instructions to cells on how to make fungal proteins, triggering an immune response. The review discusses how to optimize these vaccines, what challenges need to be overcome, and why they might be especially useful for people with weakened immune systems who are most vulnerable to serious fungal infections.

Background

Despite intensive efforts in medical mycology, developing effective vaccines against invasive fungal infections remains challenging due to large antigenic repertoires, complicated fungal life cycles, and immune evasion mechanisms. The success of mRNA vaccines against SARS-CoV-2 has opened new possibilities for exploring mRNA-based approaches for antifungal vaccine development.

Objective

To discuss recent advancements and key scientific areas that need exploration to develop effective antifungal mRNA vaccines delivered via lipid nanoparticles (LNPs), addressing challenges specific to fungal pathogens and immunocompromised populations.

Results

The review identifies key advantages of mRNA-LNP vaccines including non-integrating properties, proper post-translational modifications, and manufacturing scalability. It highlights barriers such as high costs, short duration of protection, glycosylation divergence between fungi and mammals, and vaccine hesitancy.

Conclusion

mRNA-LNP vaccines represent a promising platform for antifungal vaccine development with optimization of UTRs, LNP delivery, adjuvants, and specialized approaches for immunocompromised hosts. Heterologous prime-boost strategies combining mRNA and subunit protein vaccines may enhance immune responses against fungal infections.
  • Published in:PLoS Pathog,
  • Study Type:Review,
  • Source: PMID: 40293964
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