Plasmodium falciparum serine repeat antigen 5 (SE36) as a malaria vaccine candidate

Abstract

A devastating disease spread by mosquitoes with high-efficiency, malaria imposes an enormous burden for which no licensed vaccine currently exists. Although the genome complexity of the parasite has made vaccine development tenuous, an effective malaria vaccine would be a valuable tool for control, elimination and eventual eradication. The Plasmodium serine repeat antigen 5 (SERA5) is an abundant asexual blood stage antigen that does not show any antigenic variation and exhibits limited polymorphism, making it a suitable vaccine candidate. Identified by comparing the IgG status of people in endemic areas with protective immunity and those with malaria symptoms, the vaccine potential of the N-terminal domain of Plasmodium falciparum SERA5 is also strongly supported by experimental data and immune responses both measured in vitro and in animal challenge models. The current understanding of SERA5 will be presented, particularly in relation to its path towards clinical development. The review highlights lessons learned and sorts out issues upon which further research efforts are needed.

Introduction

World Malaria Report 2010 [1] documents a decrease from previous years (2000–2008) of malaria burden to 225 million cases and a large absolute decrease in death to 781,000 in 2009. For the first time not a single case of falciparum malaria was reported in the WHO European Region. This was attributed to the accelerated drive against malaria since 2008 which drew increased funding for the procurement and distribution of artemisinin-based combination therapy (ACT), insecticide-treated bed nets (ITNs), intermittent preventive treatment (IPT), as well as other mosquito vector control strategies (e.g. indoor residual spraying, IRS). The interventions produced measurable public health impact resulting to a reduction of more than 50% in either confirmed malaria cases or malaria admissions and deaths in 11 countries and one area in the African Region. The heaviest toll, however, is still reported on poor and vulnerable populations where the disease continues to constitute an unbearable burden on the already overstretched health services particularly in Africa. Total global spending on malaria was estimated to be about US$ 3000 million in 2009 [2]. Notably, in the same year, resurgences of malaria were observed in Rwanda, São Tomé and Príncipe, and Zambia. The burden of malaria was reportedly underestimated in India [3]; and in some regions malaria incidence continues to increase or remains highly variable [4], [5]. Additionally, lines of evidence have been accumulating very recently that Plasmodium falciparum parasites on the Thai-Cambodian border are less effective to ACTs after 10 years of the drug therapy [6]. ATCs, ITNs and IRS are, likewise, likely threatened by the inevitable emergence of insecticide-resistance given that malaria vector control is highly dependent on a single class of insecticide and the widespread implementation of these interventions are highly dependent on poor health infrastructure of many malaria-endemic countries. The year was also marked with observations of great apes as possible reservoirs of P. falciparum [7], [8] and Plasmodium knowlesi infections in Thailand [9]. P. knowlesi, considered previously only as a malaria species of macaque monkeys, is the fifth Plasmodium species to cause malaria in humans. An effective vaccine would thus, undeniably, provide a viable tool if we are to realize the vision of a global malaria eradication program.

Experience has confirmed that development of malaria vaccines presents formidable difficulties. Complexities relate mainly to the complex parasite biology, gaps in understanding immune response, pre-clinical, clinical and field vaccine evaluation [10], [11]. Nevertheless, WHO calls for support and strong links for the development of a malaria vaccine with 80% efficacy for inclusion within the context of WHO-recommended malaria control measures [2], [12].