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Edible Algae as a Vaccine Vector
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Malaria is one of the top three leading causes of death due to infectious disease worldwide. As many as 300 million people are infected with malaria worldwide every year, resulting in an estimated one to three million deaths. Malaria is caused by several parasites of the genus Plasmodium, with P. falciparum being responsible for most of the deaths. While antimalarial therapies are available to help those who are infected, a protective vaccine against malaria is still urgently needed. Because malaria mostly affects people in poverty stricken areas, the vaccine should be cheap and easy to administer. This would help maximize compliance and be best at preventing disease.

Malaria is a protozoan parasite, which means it is caused by a eukaryotic pathogen. Bacteria, which are often used to produce proteins for vaccine constructs, are prokaryotic, and lack much of the complexity of the eukaryotic cell. The bacteria are not able to process proteins in the same fashion that eukaryotes can, making it difficult to develop a properly folded and processed malaria protein in a bacterial vector. If the proteins produced by the bacteria are not identical to the proteins produced by malaria parasites, they will not be recognized by the immune system. This has hampered anti-malaria vaccine production. A eukaryotic vector would be a better candidate, as it would have to proper machinery to process the proteins so that they are identical to the malaria-produced proteins.

A team of researchers at the University of California at San Diego have attempted to make an edible vaccine against malaria. They engineered algae to produce a protein from P. falciparum that has strong immunogenicity in mice. In addition, the researchers engineered the algae to produce a protein from Vibrio cholera, which would be fused to the P. falciparum antigen. The V. cholera protein sticks to intestinal cells. The researchers wanted the engineered fusion protein from the algae to be taken up by the intestinal cells and presented to the immune system within the gastrointestinal tract. When mice were fed the freeze dried algae, they produced substantial amounts of IgA antibody against the P. falciparum protein. IgA is an isotype of antibody that is primarily produced by mucosal immune responses, and is effective against pathogens that infect the mucosae.

Malaria, however, is injected into the blood stream via the bite of a mosquito. The malaria parasite first goes to the liver, where it develops into a form that can then infect red blood cells. The IgA antibody produced by the mice in response to the edible algae vaccine would be ineffective against malaria parasites. IgG antibodies, which are produced in the blood stream, are considered to be more effective against malaria infection by many researchers. Learning how to develop the proper antibody response is one of the important aspects of vaccine production. Improper antibody responses would not be effective at preventing infection.

Even though the vaccine construct does not appear suitable for use against malaria, the researchers are hopeful that it can be used against a variety of mucosal diseases. Many viral and bacterial infections are food borne; they enter the host through the digestive tract. In these cases, a mucosal IgA antibody response produced in the gastrointestinal tract would be very beneficial. The edible algae vaccine vector could be used against such food borne pathogens as Salmonella and E. coli.

While it might seem unusual at first to consider using an oral vaccine, which would target immune cells in the digestive tract, against a pathogen that infects blood cells, the concept is not as far out as one might think. The mucosal immune system and the systemic immune system are connected. Food digested in the gastrointestinal tract is transported to the blood in order to be delivered to other cells in the body. The same is true of antigens. Research has previously demonstrated that certain mucosal vaccination routes, such as a nasal vaccine, can be very effective at eliciting strong systemic immune responses. In fact, the researchers in the above study were able to detect blood IgG antibodies against the V. cholera portion of the fusion protein. This demonstrates clearly that the construct can induce systemic immune responses. The researchers, however, are not sure why the mice did not produce IgG antibodies against the malaria protein.


References:

http://www.sciencedaily.com/releases/201...132607.htm
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