Osaka University Immunology Frontier Research Center

Hemozoin: Malaria's Built-In Adjuvant and TLR9 Agonist

  While whole-parasite vaccine strategies for malaria infection have regained attention, although their immunological mechanisms of action remain unclear. We found in this study that:

1. Crude extract from blood stages of P. falciparum is effective as a whole blood-stage parasite vaccine via TLR9.
2. The malarial heme-detoxification byproduct, hemozoin, but not malarial DNA, acts as a 'built-in' adjuvant.
3. Both synthetic and natural hemozoin bind directly to TLR9 and induce conformational changes in the receptor.
4. The adjuvant effect of synthetic hemozoin depends on its method of synthesis and particle size.
5. Natural and synthetic hemozoin use different receptors for their adjuvant effect
6. The adjuvant function of synthetic hemozoin was further validated in a canine anti-allergen vaccine and malaria vaccine models. Hemozoin, both in synthetic and native form, can influence adaptive immune responses to malaria infection, and may have therapeutic value in vaccine adjuvant development.