Prospects for new Malaria vaccine | Jotted Lines

Malaria is one of the most deadly pandemics to threaten human health. It consumes tens of thousands of lives each year in sub-Saharan Africa, most of who are young children. For example, each year close to 400 million people are infected with the disease, of which a million succumb to it. Hence all efforts must be channeled to find a robust vaccine for preventing it. Hence, research in this area is going at an intense pace in recent years. But unfortunately, there are no foolproof vaccines that have been formulated yet. A vaccine by name RTS S/AS01, which was put to trial during 2009, is specifically addressed to vulnerable children in the Third World. One of the reasons why formulating vaccines have proved challenging is due to the constantly adapting nature of malaria parasites. The latter either evolve drug-resistance or the mosquitoes themselves constantly change and become insecticide resistant. It is in this context that the thrust of new research should be based. The article by Anthony Watts, posted in his website ‘Watts Up With That?’ presents recent discoveries in this area. The article is a summary of the research paper presented in the journal Proceedings of the National Academy of Sciences USA in September of 2010. Usually, malaria parasites use certain pathways to infect human cells. The identification of one such key pathway is believed to provide scientists will crucial leads. The research team at Walter and Eliza Hall Institute has been credited with this identification. They now believe that a new vaccine target can be produced, through which contact with malaria could be avoided. The most lethal form of malaria is caused by the parasite Plasmodium Falciparum. The ability of this parasite to invade red blood cells through numerous channels is what makes it difficult to contain. It is conventional knowledge that the parasites enter red blood cells by using proteins called glycophorins. What the researchers found is another way through which the parasite enters red blood cells. This pathway “does not involve glycophorins, instead requiring the binding of a parasite molecule named PfRh4 to Complement Receptor 1 (CR1), a common protein found on the surface of red blood cells. PfRh family of surface proteins is involved in the recognition of red blood cell receptors, which allows the parasite to attach to the red blood cell surface and gain entry.” (wattsupwiththat.com, 2010) Professor Alan Cowman, who leads the research project at Walter & Eliza Hall Medical Research Institute, offers more insights into the identified mechanism. For example, he thinks that the malaria parasite uses this protein as a guide. The protein helps the parasite identify red blood cells upon which it can attach itself. Cowman reckons that the PfRh4-CR1 pathway is key for successful entry of malaria parasites into RBC. By virtue of this discovery, biologists can now device the ideal combination of proteins to serve as a vaccine. It is believed that by blocking both glycophorin and CR1 pathways, the chances of malaria infection is nearly eliminated. These results indicate “that if a vaccine were to stimulate the immune system to recognize and generate antibodies to the prevalent invasion pathways, there is a good chance it would lead to a significant decrease in malaria infection.” (wattsupwiththat.com, 2010) This area of research is still in its infancy and pending robust clinical longitudinal trials. Paralleling the work done by the Walter and Eliza Hall Institute of Medical Research, a team in Michigan State University has created a malaria vaccine, which combines the “use of a disabled cold virus with an immune system-stimulating gene – that appears to increase the immune response against the parasite that causes the deadly disease.” (www.news-medical.net, 2011). Similarly, another group of researchers under the mentorship of Andrea Amalfitano of the College of Osteopathic Medicine have discovered a immune-system stimulating agent. But unfortunately, this agent has proven more effective in enhancing immune responses to diseases like HIV when compared to Malaria. But when the inferences of both these advancements are combined, scientists are equipped with knowledge to develop efficacious vaccine platforms for diseases including malaria. The project led by Amalfitano tries to target a particular gene on the malaria parasite – a protein called Circumsporozoite Protein (CSP). This protein is believed to act in such a way as to provide an immune resistance to malaria parasite. Those subjects that have a past medical record of malaria infection naturally develop immune resistance to this protein, implying its potential as a vaccine. Essentially, what the researchers are trying to do is to enhance the potency of the vaccine to develop immune resistance to the protein. By adding select key genes to the vaccine, the immune system gets a boost – “those genetic agents, similar to chemical adjuvants, are stimulants that improve the ability of vaccines to induce beneficial immune responses in general... In mouse models, the researchers used two such "gene-adjuvants": rEA and EAT-2, both of which aimed to illicit improved immune responses to the malaria CSP gene. Surprisingly, the rEA agent - which was developed at MSU in part by the late Barnett Rosenberg - did not produce the desired result and in fact seemed to worsen the animal's ability to generate an immune response to CSP. However, the EAT-2 gene-adjuvant stimulated the immune system in a different way, and Amalfitano and his team were able to increase the ability of the immune system to respond to CSP to a level that surpassed currently available malaria vaccine systems” (www.news-medical.net, 2011) Although these results were not what the researchers were expecting, they were able to reach their goals ultimately. The results hold promise for manufacturing a viable vaccine in the near future. According to Amalfitano, “While the way that rEA is trying to stimulate the immune system may not be the best way for malaria, we did come up with an alternative adjuvant to effectively target the parasite." (www.news-medical.net, 2011) The researchers are now keen to see whether malaria could be thwarted in animal models using the EAT-2 gene-adjuvant. This experiment is of great value, as the inferences arrived therein could help kick-start vaccine trials on humans. In conclusion, there is much promise in recent research developments towards formulating a robust malaria vaccine. But, it must also be remembered that malaria has re-surfaced in regions that it were thought to be eradicated. The condition in Sub-Saharan Africa continues to be gloomy, with children being the most susceptible to the diseases. Sociologists have also recently identified interesting correlations between malaria outbreak and general quality-of-life parameters. They have found that improving socio-economic parameters also plays a crucial role in reducing occurrences. Hope also lies in the fact that those populations that are already exposed to a malaria outbreak develop a natural immunity to the disease. Hence a comprehensive malaria eradication program will have to be devised, that not only supplies robust vaccines but also addresses the socio-economic indicators of the target locality. Making the vaccines economically affordable is another criterion for successful eradication. Vast amounts of human and economic resources are required for eradicating malaria. And as things stand now, such resources are inadequate. The initiation of The Global Fund to Fight AIDS, Tuberculosis and Malaria is an endeavor towards this end. What is now required is a sincere implementation of this program along with an expedited research on new vaccines. A co-operative effort from government agencies, philanthropic organizations (such as The Bill and Melinda Gates Foundation), Non-Governmental organizations and the pharmaceutical industry is the need of the hour. Upon the successful cooperation of these entities depend the lives of thousands of impoverished people in the world. Works Cited: MSU creates new malaria vaccine with immune-stimulating gene, retrieved from , posted on September 27, 2011 New discovery may lead to a malaria vaccine, retrieved from , posted on September 27, 2010

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