In-life Chemical Inactivation of Plasmodium Parasites by Cabamiquine Induces Long Lasting Immune Protection

Area of Science:

• Malariology
• Immunology
• Pharmacology

Background:

• Malaria is a significant global health issue with limited vaccine efficacy.
• Current malaria control relies on interventions with varying effectiveness.
• Cabamiquine (CBQ), a Plasmodium translation elongation factor 2 inhibitor, shows potential for malaria treatment and immunity induction.

Purpose of the Study:

• To assess CBQ-based infection-and-treatment strategies for inducing protective immunity against Plasmodium.
• To evaluate CBQ's efficacy in mouse models during both liver and blood stages of malaria.
• To determine if CBQ can elicit durable immune responses against homologous and heterologous Plasmodium challenges.

Main Methods:

• Mice were treated with a single oral dose of CBQ during liver-stage Plasmodium infection.
• Mice received CBQ combined with pyronaridine during blood-stage infection.
• Treated mice were subsequently challenged with Plasmodium parasites to assess protective immunity.

Main Results:

• CBQ treatment during the liver stage induced lasting immunity against homologous and heterologous sporozoite challenge.
• CBQ treatment reduced disease severity and was linked to liver-resident memory CD8+ T cells.
• Combined CBQ and pyronaridine treatment during the blood stage elicited stage-specific immunity, limiting parasitemia and protecting against severe malaria.

Conclusions:

• CBQ facilitates chemical inactivation of Plasmodium parasites in vivo while promoting long-lasting protective immunity.
• CBQ-based infection-and-treatment provides a proof-of-concept for a simple oral strategy.
• This approach could supplement existing malaria vaccination and control efforts.