Variable long-term protection by radiation-, chemo-, and genetically-attenuated Plasmodium berghei sporozoite vaccines.

Long-term protection against malaria remains one of the greatest challenges of vaccination against this deadly parasitic disease. Whole-sporozoite (WSp) malaria vaccine formulations, which target the Plasmodium parasite's pre-erythrocytic stages, include radiation-attenuated sporozoites (RAS), early- and late-arresting genetically-attenuated parasites (EA-GAP and LA-GAP, respectively), and chemoprophylaxis with sporozoites (CPS). Although all these four vaccine formulations induce protective immune responses in the clinic, data on the longevity of the antimalarial protection they afford remain scarce. We employed a mouse model of malaria to assess protection conferred by immunization with P. berghei (Pb)-based surrogates of these four WSp formulations over a 36-week period. We show that EA-GAP WSp provide the lowest overall protection against an infectious Pb challenge, and that while immunization with RAS and LA-GAP WSp elicits the most durable protection, the protective efficacy of CPS WSp wanes rapidly over the 36-week period, most notably at higher immunization dosages. Analyses of liver immune cells show that CD44

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Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Diana Moita reports financial support was provided by Fundacao para a Ciencia e Tecnologia. Miguel Prudencio reports financial support was provided by la Caixa Foundation. Miguel Prudencio reports financial support was provided by GSK OpenLab Foundation.