Immunity to asexual blood stage malaria and vaccine approaches

Abstract

SummaryThe development of a malaria vaccine seems to be a definite possibility despite the fact that even individuals with a life time of endemic exposure do not develop sterile immunity. An effective malaria vaccine would be invaluable in preventing malaria-associated deaths in endemic areas, especially amongst children less than 5 years of age and pregnant women. This review discusses our current understanding of immunity against the asexual blood stage of malaria -the stage that is responsible for the symptoms of the disease -and approaches to the design of an asexual blood stage vaccine.Keywords: asexual blood stage, malaria, vaccine. Malaria and Plasmodium life cycleMalaria, a parasitic infection, is an important cause of mortality and morbidity in many parts of the world. Each year, an estimated 300-500 million people are affected worldwide. In reality, the true figure could be greater than three times this number. 1 Malaria kills 1-2 million people each year, mostly children under the age of 5 years and a significant number of pregnant women in sub-Saharan Africa. 2 It is a devastating infectious disease that not only affects the health system, but also slows the rate of long-term economic growth and development. The emergence of drug-resistant strains of the parasite has exacerbated the situation, and global climate change, disintegration of health services, human migration and population displacement have also contributed. 2 In recent years, there have also been more cases of malaria in travellers to endemic countries.Malaria is caused by unicellular protozoan parasites of the Plasmodium genus. 3 There are four species of malaria parasites that infect humans: P. falciparum, P. vivax, P. ovale and P. malariae. The most severe form of malaria is caused by P. falciparum. The severity of the disease depends largely on the species and strain of the infecting parasite, and the immunological status of the person who is infected.Cyclical fevers are the hallmark of malaria and typically occur shortly before or at the time of red blood cell (RBC) lysis as schizonts rupture to release new infectious merozoites (see below). This occurs every 48 h in P. vivax, P. ovale and P. falciparum, and every 72 h in P. malariae infection. Intense fever is accompanied by nausea, headaches and muscular pain, amongst other symptoms. In patients infected with P. vivax and P. ovale, relapse may recur months to years after initial infection. This is caused by re-activation of the silent liver-stage form of the parasites (hypnozoites). Renal failure, hypoglycaemia, hepatic dysfunction, severe anaemia, pulmonary oedema, convulsions and shock are complications in severe malaria. Cerebral malaria is a frequent presentation of severe P. falciparum infection and has been attributed in part to the unique ability of the parasites to alter the surface of infected RBC so that they bind to endothelial surfaces causing obstruction of cerebral blood flow. 4 Recent observations suggest that pro-inflammatory cytokines and nitric oxide induced by p...

Immunomodulatory effects of recombinant BCG expressing MSP-1C ofPlasmodium falciparumon LPS- or LPS+IFN-γ-stimulated J774A.1 cells

“…A strong innate immune response is important in early bloodstage malaria infection to prevent the parasite from entering human red blood cells and cause disease, while strong adaptive immune responses may protect against malaria by inhibiting merozoite invasion of erythrocytes as well as enhance clearance of infected erythrocytes from the circulation. 53,54 The mechanism by which rBCG induces more inflammatory response than parental BCG and LPS is not yet known. A previous report showed that glycosylphosphatidylinositol (GPI) anchors of merozoite membrane proteins released from rupturing malaria-infected erythrocytes capable to induce low levels of TNF-α production in macrophages.…”

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

“…Anti-Plasmodium antibodies can prevent merozoites of infecting new red blood cells (RBCs), block cytoadherence to endotheliar capillary of infected RBCs (iRBCs), and promote phagocytosis by mononuclear cells [16,23,24]. However, persistence of significant levels of antimalarial antibodies relies on the continuous challenge resulting of chronic exposition to infection [3], probably as consequence of the impaired establishment of B cell memory [19].…”

Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies

“…Antibodies are believed to be an important component of acquired protective immunity, in addition to other factors (2). During blood-stage replication, P. falciparum merozoites invade erythrocytes, and antibodies that inhibit invasion and subsequent replication are believed to be important in mediating both acquired immunity and immunity generated by candidate blood-stage vaccines (3)(4)(5). However, the targets of acquired inhibitory antibodies are largely undefined.…”