Dr Gabriel UguruMonoclonal antibodies:
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Monoclonal antibodies are special antibodies made from unique white blood cells or proteins. They are designed in most cases, to target only one substance, and are being employed as carriers to deliver drugs and other substances to cancer cells.
Gametes are the sex or reproductive cells seen in the malaria parasites, while gametocytes are the sexual stages of the parasites. The gametes (male and female gametes), mediate the transmission of malaria parasites from human hosts to mosquitoes through sexual recombination to produce new haploid progenies. At this stage, no clinical manifestations of malaria are seen until the asexual blood stages.
- Malaria-transmission-blocking vaccines (TBVs) are new toolkits for controlling malaria infections. They are designed to target the key stages of the parasites of Plasmodium falciparum infection in mosquito vector (i.e. they target the gametes). The idea here is to render the carrier mosquitoes plasmodium-free and by so doing mitigate against malaria infections in humans.
A protein called Pfs230 is found on the surface of the malaria P. falciparum gametocytes and gametes. This protein is important in binding of the microgametes (male gametes) to red blood cells. Without this important step in the development of the parasites, they cannot enter into the red blood cells or complete their development.
Monoclonal antibodies developed from mice against this important protein, Pfs230, were successful in binding to the gametes and thereby blocked the transmission of the malaria parasites to mosquitoes. Scientists from the US have recently reported in Nature Communication, developing a monoclonal antibody raised against the human version of the protein, Pf230, and using it to block the transmission of the parasite into mosquitoes by targeting the sexual stage of the parasites.
- A Plasmodium falciparum sporozoite surface protein called, circumsporozoite, is required by the parasite for movement and invasion of liver cells. These cells are called hepatocytes and are important in host metabolism, detoxification and protein synthesis. A recent study published in The New England Journal of Medicine reported the development of a neutralising monoclonal antibody infusion designed to target the infectious stage of the P. falciparum sporozoites before they can reach the liver.
The study was conducted in adults who had never had previous malaria infection or vaccination. They range from 18 to 50 years old. The vaccine called CIS43LS, was administered intravenously as subcutaneous administration was difficult to evaluate. Fifteen subjects participated in the study with nine receiving the vaccine before all the volunteers were exposed to mosquito bites. The nine vaccinated subjects did not develop any malaria symptoms whereas five out of the remaining six volunteers who did not receive the vaccine, went ahead to develop malaria. The protection lasted for between 6 and 9 months.
The drawback to this experiment is the small number of participants involved and the high cost of monoclonal antibody vaccines. However trials are underway in Mali which would amongst other things, determine the protective efficacy of the vaccine against P. falciparum. Bulk production of the vaccine is also expected to lower the cost, and the protection from intravenous administration shown in this study is a conceptual proof that in a controlled infection, passive administration of monoclonal antibodies does prevent malaria.
- A new strategy to preventing malaria infections in children:
The very young are more susceptible to malaria due to the fact that their immune systems are still undeveloped compared with adults. A new approach to preventing child infections and mortality from malaria was published recently in The New England Journal of Medicine. In the study, 6,000 children under 17 months from Burkina Faso were given three doses of an anti-malaria vaccine, RTS,S (already described in previous article) and an anti-malaria drug. This was done during the rainy season when mosquitoes are known to multiply. The trial was conducted for over three years during which a booster dose was applied before subsequent rainy seasons. The trial found that with this approach, infections from malaria was cut down to as much as 70% in children compared to when vaccines or drugs were administered alone. A combination of vaccine and drug was effective because the vaccine targets and kills the malaria parasites, which multiply quickly in the liver; while anti-malaria drugs target parasites in the red blood cells. This synergistic (cooperation) approach between a vaccine and anti-malaria drug could save thousands of lives from malaria.
Currently ca. 740,000 children from Kenya, Malawi and Ghana have been vaccinated against malaria as part of routine childhood-vaccination programme.
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