By Angelika Kren, Checkbiotech

In a phase 1 clinical study, a research team has tested the efficacy of an oral vaccine produced by transgenic corn, obtaining encouraging preliminary results.

In developing countries, many people fall ill with, and eventually sometimes even die of, diseases they could have been easily protected from with today’s available medical means such as vaccinations. However, access for these people to vaccination often is restricted for logistical and financial reasons.

The production of vaccines, or vaccine antigens respectively, by common technology is very expensive. Scientists around the world work on technologies for the production and formulation of vaccine antigens in alternative systems.

The production of a vaccine antigen in transgenic plants seems to be one of the most promising approaches with advantages towards the production in bacterial, fungal, insect or other cell cultures. First off, it is inexpensive, when compared to traditional methods. Second, if the vaccine is produced in a plant, it might also function as an oral vaccination. This is an important factor for people living in developing countries that have never seen a vaccination before—for them, a needle stuck under their skin can be a rather fearful event.

In her work published in the journal “Vaccine” early this year, Dr. Carol O. Tacket and her team from the University of Maryland School of Medicine, tested whether an antigen (LT-B) produced and delivered by transgenic corn would be well tolerated and could stimulate antibody immune responses.

Escherichia coli (E. coli) is a bacterium that is a common inhabitant of the human intestine and normally, E. coli does not cause disease. However, some strains can produce toxic proteins (toxins) causing various illnesses, as for example cholera. Enterotoxic E. coli produces the heat-labile enterotoxin (LT) that causes watery diarrhea among young children in developing countries and travelers.

The structure and mode of action of LT is very similar to the Cholera Toxin. LT consist of two subunits, LT-A and LT-B. Whereas the enzymatically active LT-A subunit is the one actually causing the disease, LT-B (the binding subunit) is an enzymatically inactive protein and does not cause any pathological situations, but is highly immunogenic. Hence, LT-B potentially represents a very good vaccine antigen that is safe for humans.

Dr. Tacket’s team prepared the transgenic corn, as defatted corn germ meal, using standard commercial techniques. Thirteen volunteers were then fed doses of transgenic corn meal (9 persons) or, a control (4 persons) of defatted corn germ meal for three times that did not contain LT-B.

What Dr. Tacket found was seven (78%) of nine volunteers developed significant rises in serum IgG anti-LT-antibody and four (44%) out of nine developed significant rises in serum IgA anti-LT. Furthermore, seven (78%) out of nine vaccines developed specific IgA antibody secreting cells (ASC) and the same seven also developed IgG ASC. These results indicate that LT-B produced in transgenic corn is well-tolerated and immunogenic in humans.

But what might be the reasons for some people not responding? “There are several explanations possible,” said Dr. Tacket.

“The antigen might have been damaged while passing through the stomach and intestine. High levels of pre-existing immunity might be another explanation for non-responders, and, of course, you can never rule out genetic factors.”

At the moment Dr. Tacket’s team is working on ensuring that a larger percent of people is immunized. To increase the efficacy of the vaccine, Dr. Tackets team is looking at a variety of adjuvants that can be attached to LT-B. Adjuvants are substances that help enhance the pharmacological effect of a drug, or increase the ability of an antigen to stimulate the immune system.

Until Dr. Tacket’s new vaccine will actually be commercially available, she noted there is still some more work that needs to be done, “These are phase 1 safety and immunogenicity studies. Phase 2 safety and immunogenicity studies in larger numbers of people and phase 3 efficacy studies in the filed must be done, we do not know yet whether the anti-LT response is actually protective.”

She hopes, though, that society might benefit from her research by successfully using the transgenic corn for the production of very safe and inexpensive vaccines.