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Fungal vaccines: so needed, so feasible, and yet so far off

Summary

Fungal infections kill millions of people worldwide each year, particularly those with weakened immune systems, yet no vaccines exist to prevent them. Scientists have discovered that a specific fungal enzyme called Eng2 can trigger protective immune responses against three major disease-causing fungi. A vaccine containing this enzyme from all three fungi species could potentially protect against multiple dangerous fungal infections, though challenges like cost and the need to work in immunocompromised patients remain before such vaccines reach patients.

Background

Invasive fungal infections cause significant morbidity and mortality with 3.8 million deaths worldwide annually, yet no licensed vaccines exist to prevent any fungal disease. The prevalence of fungal diseases is increasing due to rising numbers of immunocompromised individuals and the ongoing HIV pandemic. Fungal diseases are generally difficult to diagnose and treat, requiring prolonged antifungal therapy.

Objective

To discuss the feasibility and challenges of developing fungal vaccines, with focus on recent findings about endoglucanase 2 (Eng2) as a shared antigen among pathogenic fungi. The paper examines the potential for a pan-fungal vaccine strategy and addresses barriers to vaccine development.

Results

Eng2 elicited protective immunity against Blastomyces, Coccidioides, and Histoplasma species in humanized mouse models. CD4+ T cell responses to Eng2 were identified in patients who recovered from these infections. Species-specific homologous Eng2 protected against respective fungal species, though sequence variation prevented cross-protection between species.

Conclusion

A polyvalent vaccine composed of Eng2 from multiple fungal species could provide pan-fungal protection. While fungal vaccines are scientifically feasible and desperately needed, economic challenges, the sporadic nature of fungal disease in immunocompromised populations, and regulatory hurdles remain significant barriers to development. Therapeutic vaccine approaches may offer an easier path to licensure than preventative strategies.
  • Published in:Journal of Clinical Investigation,
  • Study Type:Review/Commentary,
  • Source: 10.1172/JCI199451, PMC12618062
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