How can we develop an effective subunit vaccine to achieve successful malaria eradication?

Malaria, a mosquito-borne infection, is the most widespread parasitic disease. Despite numerous efforts to eradicate malaria, this disease is still a health concern worldwide. Owing to insecticide-resistant vectors and drug-resistant parasites, available controlling measures are insufficient to achieve a malaria-free world. Thus, there is an urgent need for new intervention tools such as efficient malaria vaccines. Subunit vaccines are the most promising malaria vaccines under development. However, one of the major drawbacks of subunit vaccines is the lack of efficient and durable immune responses including antigen-specific antibody, CD4⁺, and CD8⁺ T-cell responses, long-lived plasma cells, memory cells, and functional antibodies for parasite neutralization or inhibition of parasite invasion. These types of responses could be induced by whole organism vaccines, but eliciting these responses with subunit vaccines has been proven to be more challenging. Consequently, subunit vaccines require several policies to overcome these challenges. In this review, we address common approaches that can improve the efficacy of subunit vaccines against malaria.