Proposed end-users
China itself is a big country of HFMD; there are a large number of HFMD every year, with children under the age of 5 the majority of the patients. And a few patients even lost their precious lives. With the practice of China's three-child policy, more babies will be born, which means that China will confront more HFMD cases in the future. Therefore, our target user is the newborns, and this oral vaccine is undoubtedly the best choice for them, as they can avoid HFMD while not having to tolerate the pain of injection. Our sales target falls into two categories. The first is to supply directly to the hospital and its hospital travel supply chain; The second is to sell the patent or technology to companies where resales and channels are absolutely guaranteed.
The number of monthly cases of HAND-foot-mouth disease and the proportion of the total number of infectious diseases in China in 2020
Number of cases of hand foot and mouth disease in China, 2014-2020
Product-use illustration
-
A solid sugar pill, which the child will be more likely to take without the bitter taste of the medicine.
-
A dropper, in which the vaccine is stored in liquid form and used through an inlet.
-
Solid powders, which will be taken in after mixing it with water.
-
Direct oral liquid preparation.
Our Impact
Product development:
In our project, we selected VP1, which is the main antigenic gene of the EV71 virus, as the target gene for the development of the HFMD vaccine. In order to enhance the mucosal IgA and humoral IgG responses of antigens through different immune pathways, we also designed to combine the B-subunit of heat-labile enterotoxin (LTB) to construct the plasmid before transformed into E. coli and Lactobacillus casei
Now we have already successfully obtained two kinds of E. coli strains, pGEX-6P-1-VP1 and pGEX-6P-1-VP1-LTB respectively. In addition, we confirmed the expression and antigenicity of VP1 and VP1-LTB proteins in E. coli as well as the optimum conditions of the expression. In the next stage, we will continue our partnership with iGEM team Pro-CASei to further develop the L. casei vaccine.
Distribution channel:
-
The first is directly supplied to hospitals or pharmacies, forming a supply chain with hospitals and selling as prescription drugs.
-
The second is to sell the patent or technology to major companies, in the sales volume and channel has an absolute guarantee.
Safety concern
As a Biotechnological product, there are two aspects of product security that we need to consider. First, the security of the vaccine itself. To ensure the HFMD oral vaccine's appearance on the market, our laboratory will conduct comprehensive and rigorous experiments to support the quality of our oral vaccine. Second, the compatibility of our product with other vaccines. For now, there are several legal vaccines and self-funded vaccines on the market. In order to guarantee there won't be negative influences if inoculator has had more than two vaccinations. Third, the compatibility of our product for inoculators. Because we are a monopoly in the market, we will step up to expand overseas market, for which we need to consider gene differences between different races, making sure our oral vaccine will be compatible for all inoculators of difference races.
Challenges
Firstly, the harsh environment in the GI tract. Orally delivered antigens need to overcome multiple physicochemical and biological barriers in the GI tract, for example, the biological barrier of the intestinal epithelium and its mucus-secreting layers. To accomplish digestion and absorption, the presence of mucus and proteolytic enzymes make the GI tract a highly acidic environment where proteins can be easily degraded. These characteristics can degrade VP1-LTB proteins, which interferes with the immunological effects of the vaccine. Furthermore, the majority of absorption processes only last for 3-4 hours in the small intestine, which sets a temporal limitation for the absorption of the antigens in the vaccine.
Secondly, the choice of the carriers in the vaccine. Due to the multiple barriers in the GI tract, oral vaccines are not so effective and efficient as traditional injection-based vaccines in inducing an immune response, so a higher dose of antigens is needed to induce an immune response when delivered orally. This sets another limitation on the choice of bacteria as the expressive system, as the bacteria must be capable of expressing the required antigen dosage. Besides, larger doses also increase the risk of inducing tolerance instead of stimulating a protective response. The GI tract is constantly exposed to a variety of pathogens. If a vaccine does not induce the appropriate danger signals, the body can recognize it as non-pathogenic, resulting in immune tolerance instead of immune responses. Thus, it is of paramount significance to include potent adjuvants in the carriers in the oral vaccine so that the immune system can be stimulated.
Reference
-
Vela Ramirez, J. E., Sharpe, L. A., & Peppas, N. A. (2017). Current state and challenges in developing oral vaccines. Advanced drug delivery reviews, 114, 116–131. https://doi.org/10.1016/j.addr.2017.04.008