mRNA vaccination may overcome malaria vaccine weakness caused by parasite waste buildup

Immunization with Radiation Attenuated Sporozoites (RAS) may be compromised by prior blood-stage malaria exposure, affecting CD8+ T cell responses.

• Prior exposure to blood-stage malaria weakens the immune response generated by RAS vaccination in a mouse model.
• The malarial pigment hemozoin is identified as a factor that impairs CD8+ T cell responses.
• Impaired antigen uptake by dendritic cells leads to reduced activation of T cells.
• A lipid nanoparticle-encapsulated mRNA vaccine containing CD8+ T cell epitopes can restore T cell responses in previously exposed mice.
• Combining RAS with the mRNA vaccine improves the development of liver resident memory T cells and protection in malaria-experienced hosts.

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