The role of different components of the immune system against Plasmodium falciparum malaria: Possible contribution towards malaria vaccine development

Abstract

Plasmodium falciparum malaria still remains a major global public health challenge with over 220 million new cases and well over 400,000 deaths annually. Most of the deaths occur in sub-Saharan Africa which bears 90 % of the malaria cases. Such high P. falciparum malaria-related morbidity and mortality rates pose a huge burden on the health and economic wellbeing of the countries affected. Lately, substantial gains have been made in reducing malaria morbidity and mortality through intense malaria control initiatives such as use of effective antimalarials, intensive distribution and use of insecticide-treated nets (ITNs), and implementation of massive indoor residual spraying (IRS) campaigns. However, these gains are being threatened by widespread resistance of the parasite to antimalarials, and the vector to insecticides. Over the years the use of vaccines has proven to be the most reliable, cost-effective and efficient method for controlling the burden and spread of many infectious diseases, especially in resource poor settings with limited public health infrastructure. Nonetheless, this had not been the case with malaria until the most promising malaria vaccine candidate, RTS,S/AS01, was approved for pilot implementation programme in three African countries in 2015. This was regarded as the most important breakthrough in the fight against malaria. However, RTS,S/AS01 has been found to have some limitations, the main ones being low efficacy in certain age groups, poor immunogenicity and need for almost three boosters to attain a reasonable efficacy. Thus, the search for a more robust and effective malaria vaccine still continues and a better understanding of naturally acquired immune responses to the various stages, including the transmissible stages of the parasite, could be crucial in rational vaccine design. This review therefore compiles what is currently known about the basic biology of P. falciparum and the natural malaria immune response against malaria and progress made towards vaccine development.

Keywords: Immune cells; Malaria; Vaccine candidates.

Fig. 1

Life cycle of P. falciparum showing the various stages (arbitrarily labelled 1 to 6). Various vaccine candidates have been developed and are in the process of being tried. For Stage 1 (Pf25, Pf230, Pfg27, Pfs45/48, Pfs16, Pfs28. For Stage 4, CSP-1, TRAP, STARP, SALSA, SSP-2, for Stage 5, Attenuated sporozoites RTS,S and/or AS02 with prime boost (ME-TRAP), SPF66, MuSTDO. For Stage 6 (Ring Stage: Combination B (MSP-1, MSP-2, RESA), MSP-1 and/or AS02, MSP-3 and or GLURP, AMA-1.) (Trophzoite Stage: SERA, AMA-1, RAP-1, MSP-1, MSP-2, MSP-3, MSP-5, EBA-175, RAP-2, GLURP, RESA, EMP-1, Pd35, Pf55, PfRH5). List of vaccine candidates adapted from Tongren et al., [177]. Abbreviations: AMA, apical membrane antigen; CSP, circumsporozoite surface protein; EBA, erythrocyte-binding antigen; EMP, erythrocyte membrane protein; GLURP, glutamate-rich protein; ME–TRAP, multiple epitope–thrombospondin-related adhesive protein; MSP, merozoite surface protein; Pf, P. falciparum protein; RAP, rhoptry-associated protein; RESA, ring-infected erythrocyte surface antigen; SALSA, sporozoite- and liver-stage antigen; SERA, serine-repeat antigen; SPf66, synthetic P. falciparum 66; SSP, sporozoite surface protein; STARP, sporozoite threonine- and asparagine-rich protein; TRAP, thrombospondin-related adhesive protein. Figure adapted from Winzeler, [19].