Abstract
Crude preparations of malaria parasite proteins from the hydrophobic and hydrophilic phases were made by Triton X-100 temperature-induced phase separation procedures. Cysteine protease was purified from the hydrophobic phase of the parasite protein preparation. Groups of BALB/c mice were immunized intraperitoneally with the purified cysteine protease and crude preparations of the parasite proteins respectively. Priming and booster immunizations were administered on days 0, 14 and 21 prior to lethal parasite challenge on day 30. The course of infection was monitored by microscopic Giemsa-stained, thin blood smears. Protection was conferred at varying thresholds in the groups of mice immunized. This was shown by a week delay in the onset of parasitemia and red blood cell invasion by parasites in the group of mice immunized with the purified cysteine protease. Pack Cell Volume, parasite burden and the mean survival time of mice in days post-infection when compared to experimental controls indicated that protection was conferred in mice during immunization. Our data shows that the parasite enzyme cysteine protease is a potential target which can further be exploited for precise drug targeting and vaccine development against malaria.
Highlights
Malaria is a serious disease caused by parasites of the genus Plasmodium and it is transmitted by female anopheline mosquitoes.Malaria poses a tremendous impact on human health, killing millions of people annually and it is a major impediment for social and economic development in malaria-endemic areas in sub-Saharan Africa [1]
We report the acquisition of protection in BALB/c mice by immunization with purified forms of cysteine protease against a lethal challenge with virulent strain of Plasmodium berghei
2 to 5 post -infection and reached a peak parasitemia of 67 % ± 2 on day 10 ± 2 and succumbed to infection (Figure 3), while mice immunized with purified cysteine protease formulated in adjuvant reached a peak parasitemia of 28.77% ± 0.87 on day 18 ± 4 (P=0.05)
Summary
Malaria is a serious disease caused by parasites of the genus Plasmodium and it is transmitted by female anopheline mosquitoes.Malaria poses a tremendous impact on human health, killing millions of people annually and it is a major impediment for social and economic development in malaria-endemic areas in sub-Saharan Africa [1]. After tuberculosis and HIV, malaria constitutes the single greatest threat to human health of the recognized infectious diseases in terms of annual mortality and morbidity [2]. Due to the global resistance of malaria parasites to mainstay antimalarial drugs, there is need for new approaches to malaria treatments. Among these approaches is the targeting of enzymes with essential roles in the parasite’s life cycle [3]. Proteases which appear to be required for a number of important functions in erythrocytic parasites, including haemoglobin hydrolysis, erythrocyte rupture, and erythrocyte invasion are important in the pathophysiology of malaria [4]. The best characterized proteolytic function is the hydrolysis of haemoglobin, which provides amino acids for the parasite’s protein synthesis and other necessary functions [3]
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