Can scientists rid malaria from the Third World by simply feeding algae genetically engineered with a vaccine?

That’s the question biologists at UC San Diego sought to answer after they demonstrated last May that algae can be engineered to produce a vaccine that blocks malaria transmission. In a follow up study, published online today in the scientific journal Applied and Environmental Microbiology, they got their answer: Not yet, although the same method may work as a vaccine against a wide variety of viral and bacterial infections.

In their most recent study, which the authors made freely available on the Applied and Environmental Microbiology website at http://aem.asm.org, the researchers fused a protein that elicits an antibody response in mice against the organism that causes malaria, Plasmodium falciparum, which afflicts 225 million people worldwide, with a protein produced by the bacterium responsible for cholera, Vibrio cholera, that binds to intestinal epithelial cells. They then genetically engineered algae to produce this two-protein combination, or “fusion protein,” freeze dried the algae and later fed the resulting green powder to mice. The researchers hypothesized that together these proteins might be an effective oral vaccine candidate when delivered using algae.

The result? The mice developed Immunoglobulin A (IgA) antibodies to both the malarial parasite protein and to a toxin produced by the cholera bacteria. Because IgA antibodies are produced in the gut and mucosal linings, they don’t protect against the malarial parasites, which are injected directly into the bloodstream by mosquitoes. But their study suggests that similar fusion proteins might protect against infectious diseases that affect mucosal linings using their edible freeze-dried algae.

 

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“Many bacterial and viral infections are caused by eating tainted food or water,” says Stephen Mayfield, a professor of biology at UC San Diego who headed the study. “So what this study shows is that you can get a really good immune response from a recombinant protein in algae that you feed to a mammal. In this case, it happens to be a mouse, but presumably it would also work in a human. That’s really encouraging for the potential for algae-based vaccines in the future.”

The scientists say bacterial infections caused by Salmonella, E. coli and other food and water-borne pathogens could be prevented in the future with inexpensive vaccines developed from algae that could be eaten rather than injected. “It might even be used to protect against cholera itself,” said James Gregory, a postdoctoral researcher in Mayfield’s lab and the first author of the paper. In his experiments with mice, he said, Immunoglobulin G (IgG) antibodies—which are found in blood and tissues—were produced against the cholera toxin, “but not the malaria antigen and we don’t quite understand why.”

Part of the difficulty in creating a vaccine against malaria is that it requires a system that can produce structurally complex proteins that resemble those made by the parasite, thus eliciting antibodies that disrupt malaria transmission. Most vaccines created by engineered bacteria are relatively simple proteins that stimulate the body’s immune system to produce antibodies against bacterial invaders.