Team:Shanghai high school/Implementation

1. Background/marketing research

We released both online and offline surveys to study the recent medical market and our target population. After analyzing the data, we recognized a huge need for the oral vaccine because the majority support such innovation in health care. For example, 32.48% of the respondents of our online questionnaire said that they or people around them used to be infected with rotavirus. However, only 17.52% of our respondents were vaccinated, and only 4.27% took oral vaccines. If we popularize the advantages of oral vaccines to more people, we will be able to fill in the blank and acquire many consumers. Through the offline interview, we noticed that parents have a relatively high knowledge about rotavirus, which is a positive phenomenon. If the parents understand the danger of rotavirus and the benefit of vaccination, they will take it seriously and be willing to accept our vaccine. They might also introduce the vaccines to our other target population so that more people can learn about our product.

2. Stakeholders

Our oral rotavirus vaccine's functional groups are infants and children whose ages are below three. So our target customers will be the pediatric departments of the hospitals and the parents who have kids below 3. We need to publicize our product and the rotavirus together to let the user group know the harmfulness of the rotavirus. The user group will be eager to know our product based on the propaganda since the parents are unwilling to see their kids sick. As for user acceptance, our product will favor the parents since the side effect of the oral vaccine is less than the vaccine that needs to be injected. Our product will be more accessible for the patients to take in. Without injection, the kids are delighted to cooperate with the doctors. The selling price for our vaccine will be relatively low, and the cost for the hospital to purchase the vaccine will be relatively low. So they will prefer to cooperate with us. For hospitals, if our products are developed and certified, hospitals will also order our oral vaccines in large quantities and let people go to hospitals to vaccinate oral vaccines.

3. The goal of our team

Our company was founded to develop and sell a vaccine with a richer flavor profile. However, as we did more and more research, we found that the world's highest rates of death from related diarrhea were in Africa and South Asia, where only 3% of the global vaccine stockpile is available. Thus, we decided to bring our vaccine to these countries to increase the availability of oral rotavirus vaccine in countries with poverty. At the same time, exporting a second will boost the depressed rotavirus market and inspire major vaccine companies to research more effective and lower-cost vaccines, thus giving more low-income countries or regions equal access to humane care.

4. Overall appearance and instructions

Inner packing

The inner packing of our oral vaccines is a pink container. We chose pink as the overall color because pink was favoured by the kids. The logo and team’s name are printed on the container. The bar code is located at the bottom of the container.

Here is the dimension of one inner packing:
Length – 1.8 cm
Width – 0.8 cm
Height – 6 cm

Outer packing

Our vaccines are packed individually. The front of our outer packages consists of a logo and our team name. We choose light pinks and dark pinks to make the overall appearance look aesthetic and harmonious.

Here is the dimension of one outer packing:
Length – 2.4 cm
Width – 2 cm
Height – 8 cm

The oral rotavirus vaccine contains 3 ml per bottle. One person takes one bottle each time. The vaccine should prevent at least 5.5lgCCID50 of live viruses per milliliter. The main ingredient is genetically engineered intestinal probiotics. Excipients include lactose and sucrose. The shelf life of the oral vaccine is one year. It should be kept in the dark at -2.8 degrees Celsius. This vaccine is for infants between 2 months and 3 years of age. You can feed infants directly by opening the bottle and helping them to drink.

Possible side effects

Transient mild vomiting and diarrhea, usually automatically disappearing within 2-3 days. Short fever may occur within 1-2 weeks after oral vaccination. In most time, the fever will ease after 1-2 days without treatment. If the situation gets worse, you can use symptomatic drug treatments.

5. Principle analysis of product engineering

In consideration of our primary audience, children younger than five, we aim to develop an oral vaccine that can be vaccinated in a form of a mixture with daily drinks, in this way avoiding the fierce resistance they might adopt when being injected by drugs. Since children have an immature immune system, we do not consider live-attenuated vaccines and inactivated vaccines because they include the complete form of the virus as the antigen, which could potentially be harmful to a vulnerable immune system. Nucleic acid vaccines can also lead to an overwhelming immune response, with examples of people contracting severe fever after COVID vaccination. Thus, subunit vaccine with adjuvant is what we should consider, as it guarantees its safety through using only a fraction of a virus as an antigen to prompt the development of antibodies. Adjuvant is an extra protein integrated alongside the antigen that functions to enhance the immune system and allows for fewer doses or lesser quantities of the vaccine required to obtain the desired effect.

Therefore, we are going to produce a vaccine that includes VP7, a surface protein of rotavirus, and adjuvant LTB, a subunit of Heat Labile Enterotoxin B. VP7, being the most abundant surface protein of rotavirus, is the primary antigen detected by antibodies when rotavirus enters the body. This makes it the optimal protein candidate for the vaccine. Heat Labile Enterotoxin B is a harmful bacterium that can be absorbed in intestine and cause excessive secretion of water and electrolytes from mucosal cells and lead to diarrhea, triggering a strong immune response during the process. LTB is one of its subunits, but LTB does little harm to the body. At the same time, it can trigger the same level of response when detected by antibodies.

In order to obtain the most successful protein expression, we resulted in using the popular E. Coli as the bacteria for this experiment. This is because E.Coli is known to be the most practical bacteria due to its rapid expression, inexpensive cultivation, and high yield. Nevertheless, E. Coli can be harmful to the human body if it is used excessively (endotoxin accumulation) and its proteins can only be released once the bacteria is fully destroyed. Aside from this, we also used Bacillus Subtillus for protein expression. Bacillus Subtillus has the ability to secrete numerous enzymes (subtilisin and gramicidin) to degrade a variety of substrates, enabling it to survive under continuously changing environments. Furthermore, Bacillus consumes free oxygen in the intestines which promotes the growth of beneficial anaerobic bacteria and enhances the development of immune organs. At the same time, it has excellent protein secretion abilities and prevents potential inflammations by strengthening the gut barrier.

6. Future challenge and potential risks

The biggest challenge we face currently is the acceptance of the public about the vaccine. Comparing to the three types of vaccines in the market, our vaccine has a significant distinction. Since people do not pay enough attention to the vaccine, it will be troublesome to get acceptance quickly. Additionally, since we are newly established, the establishment of a technical barrier is weak. We might be obsoleted in the competition of the main market with the big company because our R&D ability is weaker. The developed countries have listed the rotavirus vaccine as a class I vaccine and the vaccines are afforded by the government. The vaccination coverage is high and the morbidity was low. The market was stabled and it is hard for the entry of new vaccines. Because of the cost of the traditional vaccine, the low-income countries cannot afford and the supply is less than demand. The high-cost live attenuated virus vaccine and the inactivated vaccine cannot dominate the market.

Another problem is that our products are only proven to be effective in the laboratory, but they have not been tested in animals and humans. In other words, we do still have concerns about their safety, stability and the performance in the clinical trial. Therefore, there are more experiments as well as the professional advice required for developing our products.

7. Marketing plan/product superiority

Product: We're now developing an oral vaccine against rotavirus that has fewer side effects than the injectable vaccine and doesn't require an injection, so kids will be more willing to cooperate with their doctors. After completing the research and development, obtaining certification, and entering the market, we will control the price of the vaccine, reduce the cost of the hospital to buy the vaccine, and make the hospital more willing to cooperate with us.

Price: Since most of our future markets are developing countries, we will adjust the cost to a relatively low level and sell in small profits and quick turnover. One is to make it affordable for these countries, and the other is to help these countries achieve social benefits.

Location: We will promote and sell to hospitals, schools, and health organizations in different countries.

Promotion: In today's world, with the rise of we-media and the Internet, we will be promoting the dangers of rotavirus and our vaccines on major media outlets like TikTok, YouTube, etc. Offline, we will also use relatively formal channels, such as health institutions (children's hospitals, etc.), schools, and other public places. In addition, we will cooperate with major hospitals, some public welfare organizations, and charitable foundations to increase sales.