Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria

What is it about?

Malaria accounts for an enormous burden of disease globally, with Plasmodium falciparum accounting for the majority of malaria, and P. vivax being a second important cause, especially in Asia, the Americas and the Pacific. During infection with Plasmodium spp., the merozoite form of the parasite invades red blood cells and replicates inside them. It is during the blood-stage of infection that malaria disease occurs and, therefore, understanding merozoite invasion, host immune responses to merozoite surface antigens, and targeting merozoite surface proteins and invasion ligands by novel vaccines and therapeutics have been important areas of research. Merozoite invasion involves multiple interactions and events, and substantial processing of merozoite surface proteins occurs before, during and after invasion. The merozoite surface is highly complex, presenting a multitude of antigens to the immune system. This complexity has proved challenging to our efforts to understand merozoite invasion and malaria immunity, and to developing merozoite antigens as malaria vaccines. In recent years, there has been major progress in this field, and several merozoite surface proteins show strong potential as malaria vaccines. Our current knowledge on this topic is reviewed, highlighting recent advances and research priorities.

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Why is it important?

Malaria remains one of the world’s leading causes of morbidity and mortality with an estimated 600 000 deaths and 200 million cases annually. Over the past 10 years, there has been substantial progress in reducing the enormous burden of malaria globally through the use of interventions such as insecticide-treated bed-nets, improved access to early diagnosis and effective treatment of malaria including the use of highly effective artemisinin combination therapy (ACT). However, emerging resistance to ACTs, increasing mosquito resistance to insecticides, and evidence of rebound increases of malaria in some regions, highlights the need for effective vaccines, new antimalarial agents and other novel control interventions. The development of highly efficacious vaccines remains a key long-term goal. A number of merozoite antigens are promising vaccine candidates with some showing partial efficacy in clinical trials.

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