Malaria serology for surveillance, insights into immunity, and vaccine development

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ABSTRACT Malaria remains an infectious disease of global health concern. Recent approval and implementation of two vaccines for use for prevention of Plasmodium falciparum malaria in children in the African region is predicted to significantly reduce the burden of this disease. However, efforts are still required to improve efficacy and durability of these vaccines in target populations, and many other challenges remain to achieve malaria eradication. These include emergence and predominance of non-falciparum malaria in countries nearing elimination of P. falciparum , resurgences in malaria-free settings, and impacts of changing populations and ecology on transmission. Novel tools are needed to target neglected Plasmodium species, notably Plasmodium vivax, the second most common cause of human malaria. Plasmodium infections induce robust immune responses, meaning Plasmodium- specific antibodies can be used as both surveillance tools and as markers of immunity to clinical disease. In this mini-review, we discuss these use cases of malaria serology. We detail the concept behind serological surveillance and the need to understand antibody longevity, and discuss the application of this approach in endemic countries for both improved surveillance and as an intervention, with a focus on P. vivax while touching on other neglected Plasmodium species. People living in malaria-endemic areas naturally gain clinical immunity to malaria, meaning sero-epidemiological studies can also be used to understand the targets and functions of protective immunity. We review new studies on protective immunity, covering research on both P. falciparum and P. vivax , and highlight how these findings can be leveraged to maximize existing and novel vaccine design.