Malaria vaccines targeting the pre-erythrocytic stage: a scoping review

Abstract

<ns4:p>Malaria is a deadly infectious parasitic disease that causes devastating morbidity and mortality globally. Despite being a public health concern, an effective vaccine for prevention of the disease remains elusive. Global efforts are exploring possible ways of developing and improving vaccines to counteract the complex nature in which <ns4:italic>Plasmodium falciparum </ns4:italic>evades the immune system. A number of vaccines have been developed in the past targeting the various parasitic life cycle stages. Transmission blocker vaccines, such as <ns4:italic>PpPf S25,</ns4:italic> target the parasite stages in the mosquito vector. However, these herd vaccines only protect the immunized population. Vaccines targeting blood-stage forms, such as the <ns4:italic>AMA-1</ns4:italic> and <ns4:italic>MSP-1</ns4:italic> vaccines, are challenged by the complex metabolic pathways of erythrocytes and merozoites. Vaccines targeting the pre-erythrocytic sporozoite stage remain the most promising approach thus far. Here, we systematically review the literature on pre-erythrocytic stage vaccines and on-going work in the field. Furthermore, we highlight gaps in current knowledge and point to potential areas of future work. Articles on pre-erythrocytic malaria vaccines were obtained from Google scholar, PubMed and Cochrane starting from the year 2010. Ten papers were reviewed. A number of vaccines were reviewed highlighting; the vaccine type, clinical phase of trial, population demographics, vaccine immunogenicity, efficacy and safety. The <ns4:italic>RTS,S</ns4:italic> vaccine is reportedly the most advanced, having been rolled out for phase III clinical trials in a number of malaria-endemic African countries. The pre-erythrocytic vaccines discussed have made milestones in clinical trials. Some of the challenges elicited may be addressed via screening for novel antigens, exploring suitable vaccine administration vehicles,­ as well as using a combined multi-stage vaccine approach.</ns4:p>

<p>Antimalarial Drug Resistance and Novel Targets for Antimalarial Drug Discovery</p>

“…Drugs currently in Phase I, II and III trials for blood-stage treatments of malaria includes KAE609 (cipargamin) inhibit Na+-TPase 4 ion channel, 116 KAF156/GNF156/(Cyclic amine resistance unknown mechanism of locus (PfCARL) inhibitor), 117 Albitiazolium/SAR9727/(Inhibit the transport of choline into the parasite), 118 DSM265 (Inhibit dihydroorotate dehydrogenase enzyme), 119 Methylene Blue (Prevents haem polymerisation by inhibiting P. falciparum glutathione reductase), 120 Sevuparin/DF02/(Anti-adhesive polysaccharide derived Blocks merozoite invasion and sequestration), 121 MMV048 (Inhibiting the parasite enzyme phosphoinositol 4-kinase enzyme), 122 MMV390048 (Phosphatidylinositol 4-kinase (PfPI4K) inhibitor), 123 Fosmidomycin + piperaquine (DOXP pathway), Artefenomel (oz439) + Piperaquine (Synthetic endoperoxide), 124 OZ277+ Piperaquine (Inhibit Pf-encoded sarcoplasmic endoplasmic reticulum calcium ATPase), P218 (PfDHFR inhibitor), 125 M5717/DDD498/(Protein-making machinery of the malaria parasite, liver- stage P. falciparum), 126 SJ733 (The P-type Na+–ATPase transporter), 116 and Spiroindolone (cipargamin) inhibits PfATP4, a parasite plasma membrane Na+-ATPase that regulates sodium (maintains low-level Na + in the cytosol) and osmotic homeostasis. Cipargamin is used in the treatment of falciparum and vivax malaria.…”

“…Sevuparin/ DF02/(Anti-adhesive polysaccharide derived Blocks merozoite invasion and sequestration), 121 MMV048 (Inhibiting the parasite enzyme phosphoinositol 4-kinase enzyme), 122 MMV390048 (Phosphatidylinositol 4-kinase (PfPI4K) inhibitor),123 Fosmidomycin + piperaquine (DOXP pathway), Artefenomel (oz439) + Piperaquine (Synthetic endoperoxide),124 OZ277+ Piperaquine (Inhibit Pf-encoded sarcoplasmic endoplasmic reticulum calcium ATPase), P218 (PfDHFR inhibitor), 125 M5717/ DDD498/(Protein-making machinery of the malaria Targets of proteases and amino peptidase, malaria parasite detoxification mechanism. Abbreviation: PDT, possible drug targets.…”