A new vaccine against malaria has now shown promising results in mice. If its safety and efficacy are unproven in humans, its mode of administration – oral – would make him an ideal candidate for the fight against malaria.
Malaria is the most common infectious disease in the world, causing 300 m. annually to 500 million cases and one million deaths, mostly young children. While a vaccine “classic” against malaria is being developed by GlaxoSmithKline (GSK) Biologicals (already in phase 3 clinical trials), another less trivial vaccination strategy was proposed by researchers at the CNRS.
The goal is to effectively stimulate the production of antibodies against proteins of the parasite, hoping to get better results than the 30-65% efficiency of the GSK vaccine targeting antigens of Plasmodium sporozoite. This parasite causes the disease is transmitted by the Anopheles mosquito vector present in endemic areas, which makes it difficult the fight against malaria in gradually becoming resistant to pesticides.
Antigens in starch grains
In order to synthesize stable parasite antigens and immunogens, scientists had the idea to generate proteins fused to the Plasmodium enzyme GBSS (granule bound starch synthase for). It has the distinction of being contained in the grains of starch (a complex sugar plant), which confers protection against degrading enzymes for several years. This protection will be also conferred to antigens fused. Moreover, these protein complexes in starch granules are synthesized by plants and can be easily purified.
The unicellular alga Chlamydomonas reinhardtii is a model plant of particular interest because genes fused antigen may be easily and quickly inserted into the cells and purified proteins in large quantities.
The unicellular alga Chlamydomonas reinhardtii synthesizes starch grains and could easily afford to make vaccines. © www.biologypictures.net
Chlamydomonas and Plasmodium also share in common not to add post-translational modifications (N-glycosylation) of proteins synthesized, while other plants are likely to do so. This change, however minor antigens may change and thus lead to the synthesis of specific antibodies, which no longer recognize the original antigen and therefore would not be protective.
Two pieces of the parasite proteins were chosen to be fused to GBSS: AMA1 and MSP1 of Plasmodium berghei, strain capable of infecting mice. After being assured by immunolocalization that the fusion proteins were highly localized in the starch grains, scientists have immunized mice by intraperitoneal injection.
The modified starch granules confer immunity
Whatever the construction given, the better immunized mice survived infection with a lethal dose of red cells infected with parasites (10,000 cells) than control mice. The low parasitemia (the rate of parasites in the blood), which reflects the effectiveness of the immune system’s fight against the parasite, seems to be the cause of this improved survival. In addition to this already good news, the most surprising and interesting is that both the oral ingestion of different types of starch also imparts significant immunity to mice against Plasmodium berghei.
Among these results, published in the journal PLoS One, two things to remember. Firstly the fact that these constructions are immunogenic is encouraging, but these results must be confirmed in humans meet its own parasite, Plasmodium falciparum. Second, the method of preservation of the vaccine (room temperature) and its oral ingestion (syringes and avoiding possible contamination) are real advantages in tropical countries where sanitary conditions are often limited.