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

Authors

Claudia Demarta-Gatsi, Diana Moita, Diana Fontinha, Raquel Ventura, Helena Nunes-Cabaço, Thomas Spangenberg, Miguel Prudêncio

Published in

The Journal of infectious diseases. Aug 11, 2026. Epub Aug 11, 2026.

Abstract

Malaria remains a major global health challenge, and current vaccine strategies provide limited protection. Cabamiquine (CBQ), a Plasmodium translation elongation factor 2 inhibitor, arrests parasite growth during both the liver and blood stages of infection and may promote protective immune responses during controlled parasite infection.
We evaluated whether CBQ-based infection-and-treatment strategies could induce protective immunity in mouse models of liver- and blood-stage Plasmodium infection. Mice received a single oral dose of CBQ during liver-stage infection or CBQ in combination with pyronaridine during blood-stage infection and were subsequently challenged with homologous or heterologous Plasmodium parasites.
CBQ treatment during liver-stage infection induced durable protective immunity against homologous and heterologous sporozoite challenge, reduced disease severity, and was associated with liver-resident memory CD8+ T cells. CBQ administered with pyronaridine during blood-stage infection elicited stage-specific immunity that limited parasitemia and protected against severe malaria following homologous or heterologous challenge. Together, these findings demonstrate that CBQ-based infection-and-treatment can combine effective parasite clearance with induction of protective immune responses following both liver- and blood-stage infections.
CBQ enables in-life chemical inactivation of Plasmodium parasites while promoting long-lasting protective immunity in experimental malaria. These findings provide proof of concept for a simple oral infection-and-treatment strategy that could complement existing malaria vaccination and control approaches.

PMID:
42579294
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.

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