This paper was written in one of my Biology courses. This would be an example of something that you might do while studying Biology.
Oral vaccines are not a brand-new technology that is rebranding the world of modern science. In the 1960s Bruce Sabin developed and administered the first oral vaccine against Polio(1). This oral vaccine was an immense step forward as it showed that immunity didn’t have to be gained from an invasive procedure such as needles.
Oral vaccines work by introducing weakened or modified viruses into your body, usually via a liquid. The viruses are then absorbed into the lining of your intestines, nasal airway, and almost anywhere else in the digestive system(2, 3). When the weakened virus is absorbed, your body begins to react to the virus. However, since the virus is weakened, you will not get extremely sick or become paralyzed like in the case of polio. When your body reacts, your immune system will begin creating antibodies that will help fight the virus in the future.
Fungus and Oral Vaccines? How do They Relate?
Since before Columbus discovered the Americas, the fungus Ustilago maydis (Corn Smut) has infected maize and certain types of corn. This infection results in the formation of external growths on the surface of the plant as below to the right on the piece of corn(4). These growths do not kill the plant and are often enjoyed by humans as a food called Mexican truffles, an exotic global delicacy.
When Corn Smut is not infecting a plant, it is a free-living organism that can be compared to yeast. This free-living stage is easily manipulated by scientists, allowing for the growth of many genetically modified cells of this fungus at a relatively low cost(4). Due to this, Corn Smutis of high interest to be developed into a recombinant organism or an organism that possesses an external DNA sequence, often made in a laboratory, that would otherwise be unseen in nature. The connection between vaccines and recombinant DNA may seem minuscule but is in fact significant. Being able to change the DNA of an organism easily and at a relatively reasonable cost would allow the fungus to be used as a type of edible transport system for the virus to be safely incorporated into your body.
Testing Corn Smut and Oral Vaccinations
In 2015, an experiment conducted in Mexico by Margarita Juarez-Montiel, Andrea Romero-Maldonado, Elizabeth Monreal-Escalante, Alicia Becerra-Flora, Schuyler S. Korban, Sergio Rosales-Mendoza, and JuanFrancisco Jimenez-Bermont tested the possibility of using Corn Smut to make a vaccine for Cholera. They wanted to express Cholera Toxin (CTB) in a free-living Corn Smut organism. CTB is a protein that binds to cells in humans, mice, and other mammals(4). This protein causes the immune system to create antigens against cholera and a type of E. coli. These proteins can also give rise to subsequent generations of antibodies that help protect against these diseases in the future. Cholera and E. coli are bacterial intestinal diseases that can cause diarrhea and vomiting.
This experiment combined Corn Smut and CTB DNA to develop a fungus that expresses CTB proteins that when consumed can trigger an immune response to create antibodies against Cholera and E.coli. To achieve this, the experimenters completed a series of reactions to incorporate CTB protein expression into Corn Smutcells and received four different types of DNA. To begin with, they tested if the cells would reproduce and if the new DNA would affect future generations. After testing their reproducing capabilities, they found that the modified cells can produce subsequent generations with other altered cells as well as unaltered cells. This showed the potential of the low cost of the vaccine because manufacturers can reproduce numerous genetically modified colonies instead of repeating the tedious reactions needed to incorporate the genes into each cell. Using this they can grow colonies as if they were growing crops.
The next test was to determine if the cells can still infect plants and create edible Mexican truffles. They infected an 8-day seedling of corn by injecting the modified fungus into the leaves. The Mexican truffles that grew were collected and sampled. It was found that all the truffles presented the same physical appearance no matter what fungus was injected. The only difference was that the plants that were injected with modified fungus experienced truffles that expressed CTB genes.
After establishing the possibility of successfully modifying an ingestible food into a substance that contains CTB proteins, the experimenters had to test if ingesting these modified Mexican truffles would result in resistance against Cholera and E. Coli. To do this they fed freeze-dried versions of the modified truffles to eight mice. After 21 days, blood was collected from the mice and the experimenters found antibodies in all of the mice. This indicated that the oral vaccination worked, and the mice now contained the antibodies needed to fight off Cholera and E.coli
Seven days later, they tested this immunity and infected all eight mice with Cholera and examined them after about a day. The experiment found that the mice that did not receive the modified truffles almost had twice the amount of water in their intestines indicating that their symptoms (diarrhea) and immune response were worse than that of the mice that ate the modified truffles.
Oral Vaccines Aren’t Just Meant to Stop Your Fear of Needles!
Oral vaccines are not just a way to help people with a fear of needles. Introducing and developing new oral vaccines can have social and economic effects. In countries and areas that are undeveloped or have simple and incomplete healthcare systems, oral vaccines can be administered by non-medical personnel. This allows the distribution of immunity to increase at a significant rate while also reducing the cost of paying trained medical staff for injections. A non-invasive vaccination also reduces the risk of blood diseases such as HIV or malaria which are of great concern in impoverished countries with little medical support(5).
Another huge benefit is the lower cost of oral vaccines. The ingredients of oral vaccines do not need to be purified as much as normal needle vaccinations because of the significant number of beneficial bacteria in your intestines(5). Reducing the amount of purification will decrease the production cost and also decrease the amount of money coming out of your wallet and health organization’s wallets. These potential savings can be reallocated towards studying other diseases or even developing more oral vaccines
1. S. Plotkin, History of vaccination. Proc Natl Acad Sci U S A 111, 12283-12287 (2014).
2. L. W. R. L. Coppel, Oral Vaccine Delivery: Can it Protect Against Non-mucosal Pathogens? Medscape 7(6):729-738 (2008).
3. Q. Zhu, J. A. Berzofsky, Oral vaccines: directed safe passage to the front line of defense. Gut Microbes 4, 246-252 (2013).
4. M. Juarez-Montiel et al., The Corn Smut (‘Huitlacoche’) as a New Platform for Oral Vaccines. PLoS One 10, e0133535 (2015).
5. R. De Smet, L. Allais, C. A. Cuvelier, Recent advances in oral vaccine development: yeast-derived beta-glucan particles. Hum Vaccin Immunother 10, 1309-1318 (2014).