Introduction

Under the storm of Covid-19, developing the corresponding vaccines has become one of the most crucial missions.However, we also figure out some disadvantages of the conventional vaccines at the same time, so the values we gradually explored when designing the project include,

Scientific

The Phaccine was a application of our technology ”Engineered phages carrying antigen genes to express proteins in targeted bacteria.” It’s also a demonstration for researchers who are interested in adopting the technology.

Social

(Based on our survey results) Phaccine will help reduce the number of people who are wounded, affected by blood clots, allergic to needles and so on, due to human errors or the properties of traditional vaccines itself. Many refuse to get injected because of the above-mentioned reasons, leading to difficulties for society to reach herd immunity. Whereas Phaccine, our product, has none of those shortcomings.

Moral

We also care about the animals that need to be vaccinated—sometimes even more than that of humans! It’s clear that most animals fear and suffer from the traditional kind of vaccination (later proved by our visits to multiple farms), but with our product, we can not only eliminate the time or “injection fee” which farm owners have to pay, but also can take animals' moral rights into account.

All the goals aim to accomplish the ultimate purpose—save lives, which highly affect what we prioritize in our project: accessibility. Besides, we have consulted immunological professors, local doctors, farm owners, biotech companies, the public…etc, to ensure the feasibility of the project and whether our product can do good for the world. All the activities we conducted conform to the criteria(as our guidance), and also directly impact our project.

Overview

Our integrated human practices can be divided into 6 stages:

1. Establishment of our project & interviews with immunological experts

Having interviews and being lectured by Prof.Min Shiou, Jan and Prof.Wen-Wei, Chang, we were inspired that “A safer way to get vaccination is crucial, but the accessibility of a vaccine is more important when it comes to prevalence." (impacted “purpose”)

2. Market research

We made online surveys, went to street interviews, interviewed doctors, visited farm owners, and this was when we decided our product “Phaccine” will take the form of a liquid, as one farm owner mentioned “I would prefer it to be liquid than a capsule since a sick animal can starve for days, yet it can’t stop drinking water for a day.” (impacted “design”)

3. Interviews with vaccine-developing researchers and virus expert

We visited the ADIMMUNE Corporation(a Biotech company) to learn how the current vaccine manufacturing industry works and to find whether our product will be applicable once it comes out.We had an online meeting with Prof.Bor Rung, Ou, to gain suggestions on experiments when we were entering the execution part. Lastly, we had an online interview with Dr. Yu Chi, Chou from the Academia Sinica, to mentor us with the key points and techniques of modifying the bacteriophage. With their help, we successfully completed our experiment! (impacted “execution”)

4. Education & Communication

We found the concept of vaccines and viruses to be too complicated for children to understand in the street interview, thus, we came up with a board game that we then brought on educational tours to schools and even to the Science Festival held by National Museum of Natural Science. (Communication informed by silver medal human Practices)

5. Collaborations & Partnership

We met up with multiple iGEM teams, did various collaboration projects and even had a long-term partnership with iGEM CSMU Taiwan.

6. SDGs& Inclusivity

We aim to fuse the Sustainable Development Goals into iGEM as well as promote the inclusivity of the biotech industry in order to make contribution to the equality of the globe!

1. Establishment of our project & interviews with immunological experts

After making up our minds to develop a new kind of technique that can be applied to safer ways of getting vaccinations, we had interviews with two professors from Chung Shan Medical University and were inspired to develop the Phaccine.

Firstly, reaching out to Team Csmu_Taiwan, surprisingly, we found that we were both interested in Covid-19 related projects, consequently, the two of us mutually recommended our instructors—Prof. Ming Shiou, Jan from Chung Shan Medical University and Dr. Pei Hong, Chen from Mingdao High School to each other. Prof. Jan guided us in advanced immunology knowledge, so that we can have a better understanding of how to design our experiments. Simultaneously, our partnership with the team CSMU_Taiwan went on. Furthermore, we also invited Prof. Wen Wei, Chang from the Department of Biomedical Sciences of Chung Shan Medical University to lecture us about the principles behind vaccine-developing techniques. We comprehended that the new vaccine is not only safer but also more accessible to all human beings and is of importance to the whole world after the lectures. Moreover, we were inspired and encouraged by the two professors to develop oral vaccines.

1-1) Interview with Prof. Ming Shiou,Jan

In order to understand the principles behind vaccines, we’ve invited Professor Zhan Ming Xiu, an authority in the field of immunology in Taiwan, to come and give our team a speech. Immunology surely plays a crucial role in the development of vaccines, based on this aim, professor Zhan emphasized on the “Immune responses of innate and adaptive immunity”.

Firstly, Prof. Zhan introduced the infections our body has to face, including where the pathogens come from, how our body has to face antigens, and the different ways that the intruders could cause harm to an individual. Secondly, he talked about the origins of the immune cells, such as the bone marrow. Afterwards, he discussed the major differences between innate and adaptive immunity, which is, innate immunity serves as sentries in the body that alerts the adaptive immunity system. Additionally, innate immunity has no memories whereas adaptive immunity has specific memory cells. Then, we learned about the effector mechanisms of immunity that help protect our body. Most importantly, Prof. Zhan accentuated the importance of vaccines and showed figures indicating diseases successfully busted by vaccination campaigns.

After a quick recap for us of the three types of immunity, the pathogens in our body, and the regulation between various systems in the body, he focused on the details of how our body deals with infection. For instance, humoral immunity works better on flu viruses, whereas for mycobacteria, cell-mediated immunity actually works better due to the slow production of the pathogen. Later on, we drank in the mechanisms of immunological memory and its vital relation with vaccines. Finally, he answered several common questions we’ve asked about vaccines, like the various effects vaccines have on different people etc.

Heeding a theory-oriented speech, we were truly inspired and acknowledged the depth of immunology. It turned out that the T lymphocyte has much more functions than we originally thought. Frankly, the immune system is like a complex but highly organized country, with vexing units reacting with each other. Furthermore, the fact that the innovative intranasal vaccines work better than intramuscular vaccines was absolutely fascinating. We sincerely hope that one day we could also find such great ways to treat diseases. All in all, the speech was rich in knowledge and has provided us with a clear direction of our future project.

1-2) Interview with Prof. Wen-Wei, Chang

In recent years, vaccines have played an indispensable role in the world. To gain a better understanding of how it works and the origins behind it, we invited professor Zhang Wen Wei, a famous biomedical scientist in Taiwan, to give us a lecture on the topic of the trend of vaccines nowadays. This was a truly astounding experience, and we were inspired by his speech in various aspects.

Professor Zhang introduced this topic with a brief history of how vaccines came about, including the efforts of both the West and the East. As the Chinese started preventing smallpox with a unique method called “pox planting,” this technique soon spreaded towards the West via Mongolians. It was afterwards when Edward Jenner, the father of immunology, perfected the concept and created the first vaccines in the world. Afterwards, he taught us about the principles behind vaccines, and most importantly, the evolution of vaccines itself. We soon learned that vaccines could be segmented into traditional and modern ones. While mRNA vaccines, a new generation vaccine, have great potential for now and future uses, others also thrive to make the society better with the protection they provide. Lastly, he ended the session with a friendly chat with our team and left us with awesome ideas, especially ,what impressed us the most was he and prof.Jan mentioned the identical concept“A safer way to get vaccination is crucial, but the accessibility of a vaccine is more important if wanting to be prevailing.”

To sum up, prof. Zhang introduced us to the world of immunology, and opened our eyes to how various vaccines work. Moreover, his lecture provided innovations for our project, as we found out that vaccines could be presented through numerous ways, so why not come up with a system that could be applied when a new pathogen comes out? Thus, we started executing Phaccine, a system that can be applied to vaccines with efficiency, and then, the rest is history.

2. Market research

Right after establishing the project, we did market research to ensure the advantages of our oral vaccines that conventional vaccines(needle-using ones) don’t have, and tried to modify our project to suit different the demands of different communities or explore a better way to spread public awareness. In order to achieve this goal, we not only did public surveys, but also consulted with groups that are relevant or likely to be benefitted from our project, including: local doctors, poultry farm owners. Obtaining real-world advice has indeed helped our project to be connected to society.

We started to conduct both a public online survey and street interview after preliminary establishing our project title. Because the oral vaccine has never been popular and well-known in Taiwan, we were afraid that the public people might bear some misunderstanding or prejudice against Phaccine.So we would depend on the result of the survey to decide how we are going to propagate our project and product, for example, if the people who haven’t heard of the oral vaccine are a majority, them we would hold more activities associated with basic virus & vaccine know-how. Another pivotal mission for this questionnaire was to understand what kind of appearance did the public think will be better for our Phaccine?

Upon reading the results, we surprisingly found out that there were still over 20 % people have never heard of the oral vaccine–which is a quite high number for a developed country, so we made up our minds to promote simple health education and thought of those can be our potential customers.Secondly, we surprisingly discovered that more than half of the interviewees were willing to get vaccinated by oral vaccines than traditional ones after we simplified the idea of our project and explained it to them.All in all, most people had positive attitudes towards the oral vaccines, and thus, it showed a high chance for us to further spread the it.

Last but not the least, a short answer question that required interviewees to answer “what do you think is the best appearance for an oral vaccine?” About 35 % of people answered “ water” or “liquid”, 35 % of people answered “powder”, 20% of people answered “capsule”, and the rest 10 % were other inconsistent replies.Since the difference between the two was quite close, we’ve made up our minds to do more researches and to see what would be the best for our product.

2-2) Interview with local doctors

When we were attending the SDGs proposal competition held by the Department of Social Welfare (Taichung City Government) with the theme” How to reduce the elderly’s concern about getting vaccinations?” ( see more in our “SDGs” page.) We reckoned the oral vaccine can be an appropriate solution for that, but we would have to consult professionals about in what they thought of our assumption to ensure the viability and trustworthiness of our project. Luckily, we got the opportunity to interview two doctors in our communities, they were :Dr. Nian Ching, Hsiou, Dr. Ren Rong, Yang, respectively. And they did offer precious opinions to us as experienced clinical doctors.

Surprisingly, their feedback to our project are all positive and very analogous to each other , for instance, “If there is an oral vaccine option, will it alleviate the difficulty of vaccine administration?”Both replied that the oral vaccines should be more convenient and can solve a number of dilemmas in vaccine administration in Taiwan. Also, both regarded the oral vaccine should be easier to preserve and cheaper , the two properties would end up doing good for the herd community, which was crucial all over the world, as a result, they recognize our project and saw it as a novel solution for solving the elderly’s low vaccination rate before(since its risk was thought to be far less than conventional vaccines). At the end of the interview, they suggested us to visit to local farms to understand what do the animals need and the basic know the conform to their demands so that the Phaccine would be more holistic, and , it’s also important for us to educate the public that the pros of getting vaccination surely outweighs the cons, so it’s never late for you to get injection for projecting yourself and your beloved ones!

2-3) Visit to Kien Sung chicken farm

In order to further investigate target audiences’ perspectives about oral vaccines, our team has decided to consult local ranch chiefs. Surfing the internet, we found Taichung’s Kien Sung poultry farm to be the ideal location. The appointment was a success; the chief kindly responded to all of our inquiries regarding the topic before showing us around the property.

Initially, our team assumed that this visit would merely be used to grasp the farm chief's perspective on oral vaccines, but to our surprise, we were bestowed new insights. The chief provided us with information on a variety of established probiotics and edible vaccinations, noting the cost of each. After learning how vaccines function in poultry farms and the modern market, our team has a greater grasp of the potential highlights of our product and how it should appeal to consumers.

At the end of the visit, we asked him the question that remained unsolved: As a farm owner, “what do you think is the best appearance for an oral vaccine?” This is when we decided we’ll design the vaccine liquid. He provided us with a new perspective we’d never thought of before: "I would prefer it to be a liquid than to be a capsule or powder since a sick animal can starve for days yet can’t stop drinking water for a day." and this answer greatly impacted our design of the product to be liquid.

2-4) Visit to Dongmai pig farm

After examining Jiansong Chicken Farm, our group spontaneously thought about another question: how exactly are pigs in greater demand for Taiwanese vaccinations? Therefore, we made up our minds to visit Dongmai this time.

The conduction process of this event started from discussions about various topics, starting off with the price of the vaccine for pigs. The feedback that we got was a pig will be injecting a dose for orbivirus vaccines, and orbivirus is the most essential disease that requires vaccination for pigs. The vaccination will be injected on the back of the pig’s ears; without the help from a team or an organization, the owner needs to spend a day to complete the vaccination for about 500 pigs. Within our further investigation, we discovered several fatal diseases that infect pigs, such as PRRS, Circovirus, Haemophilus Parasuis. The fatality rate of these diseases in adult pigs is around 50%, and the number is way higher for piglets. Unfortunately, most of the piglets are afraid of vaccination, and many of them struggle through the process. Even though there are vaccines that can be sprayed in the nose or throat, the result is ineffective. Moreover, the advantage of our vaccine is that it only needs to be added to the feed in powder form, and it is suitable for both adult pigs and piglets.

Mr. Lai Fuji is not merely the arduous, striving owner of a pig farm who has been working in the ground for many years, but also the one who shouldered the responsibility of cultivating the next generation’s piglets for neighboring pig farms. Due to the fact that Dongmai Pig Farm breeds sows, he hopes to be able to do the best for the health of the piglets! In this way, it is a three-way victory for consumers, ranchers and animals.``In fact, it is not a matter of price, we hope that the new vaccine can be better for pigs, even if it is more expensive than the market price,” mentioned Mr. Lai. He is one of the few herdsmen who vaccinates the pigs with his own hands. With five hundred pigs in Dongmai, Mr. Lai needed to spend nearly a day to vaccinate all the pigs and take extra time to play with the piglets; as he gets older, such a life routine gradually forms a burden. Throughout the interview, we noticed that even though oral vaccines for pigs have been developed for a while, they are still doubted by some groups of people. Fortunately, we took this opportunity to explain and deliberate with Mr. Lai about the principles of our oral vaccines and to get him to let go of stereotypes. In addition, we confirmed that we understood the phages we used were modified viruses and would not be superfluously harmful to pigs. He is also willing to support the development of oral vaccines within a reasonable range of price and utility balance.

2-5) Visit to Tunghai University’s farm

Tunghai University’s department of animal science and biotechnology is one of the most prestigious in central Taiwan. As a result, we reached out to them and hoped to get a chance to discuss our project with animal professionals and also have a visit to the most advanced farm in Taichung City.

After this visit to Tunghai University, our team learned more about livestock animals, learned more about animal expertise and their hygiene measures, such as vaccination, animal husbandry and so on. This has been of great help to our research program. After interviews with the professional researchers , we learned about the immune systems and mechanisms of livestock, such as pigs, chickens, cattle, etc. Hence we can be closer to reality and more practical in the process of designing products,for example. In addition, during the visit to the farm of Tunghai University, we learned about the current situation and predicament of farmed animals, which made us more motivated to study our products to help them. We also inquired about the school's vision for the immunity of farmed animals, which enables us to conduct more in-depth research and develop technologies and products. Finally, we visited their professional animal husbandry laboratory, we recorded and photographed it, hoping to be more professional and careful when we entered the laboratory to operate the equipment. Frankly,this is an in-depth visit.

3. Interviews with vaccine-developing researchers and virus expert

After confirming that the huge demand for oral vaccines does exist, our project also entered the execution part, thus we would like to invite more experts and scholars to assist us in making sure the safety of product, understanding how the procedure of making Phaccine is distinct from conventional ones, teach us the emphasis in terms of modifying the bacteriophage.Hence, We visited the ADIMMUNE Corporation (a Taiwanese Biotech company) and met with the General Manager and leaders of the Research and Development Division.Having a online meeting with Prof.Bor Rung, Ou, a pioneer in research of animal vaccines in Taiwan, to gain suggestions when we just entered the execution part.Lastly, we had an online interview with Dr. Yu Chi,Chou ,an virus expert from the Academia Sinica(The highest research institute in Taiwan), lectured us about the emphasis when it comes to modifying the bacteriophage.

3-1) Visit to ADIMMUNE Corporation

ADIMMUNE is a very large vaccine company in Taiwan. At first, they did not expect to make an appointment for a visit, and they attach great importance to students. They also asked the general manager to come to us. We have harvested the needs and requirements for vaccines. They mentioned that other than artificial injections. Vaccines take nasal spray vaccines as an example. The customer group is only small infants in the market. As for the safety part, they have some opinions on our plan. The Sabin vaccine, such as polio, also has safety problems due to incomplete dead virus. Finally, they showed us the process of vaccine manufacturing by a large vaccine factory, which is to use chicken embryos to mass-produce influenza vaccines. Not only is the selection of eggs very strict The environment should also be very clean. This makes us feel the caution and difficulty of making vaccines. After understanding the content and ideas considered by the developers, it is very different from our original thinking mode, and we have gained a lot.

3-2) Meeting with Prof. Bor Rung, Ou

In the interview with Prof. Bor Rung, Ou, we realized the advantages of his oral vaccine with probiotics - it can pass the test of gastric acid, reduce the bad bacteria in the intestinal tract, and can coexist with the human body in the intestinal tract.

But at the same time, we also talked about some of the advantages of our vaccine:

1. There are about 5.5 million pigs in Taiwan. If we can use our oral vaccine, it will save a lot of time, manpower, cost, etc.

2.For third world countries, the vaccination rate of some vaccines is less than 10%; our vaccines can not only reduce manpower and medical waste, but even because phage can be stored at room temperature, no refrigeration equipment is required for transportation and storage, reducing costs.

We hoped to gain suggestions when we just entered the execution part, which was when we had a meeting with him, and after deep discussion ,he thought what we needed to pay attention to the most was tackling the bacteriophage, so he told us to interview a phage expert would probably better for ensuring our safety considerations.

Finally, we would like to thank Professor Ou for his professional insights and suggestions. Because of you, our igem project has become more and more late. Thank you!

3-3) Interview with Dr. Yu Chi, Chou

After hearing the advice from Dr. Ou, we reached out to Dr. Yu Chi, Chou, who served as a researcher in Academia Sinica (The highest national research institute in Taiwan) and specialized in Virology, to have a meeting with us focusing on biotech, our project and bacteriophage.

In the beginning, we asked Dr.Chou if it was possible to develop a new type of vaccine based on phage engineering technique. He said that he thought of a nasal spray vaccine, which can produce antibodies in our upper respiratory tract, but he couldn’t make sure if those antibodies created in our gastrointestinal tract can protect us. (The nasal spray was said to have lower efficacy). He said he thought our project is theoretically viable , and also worth developing.

Then , it was in this pivotal meeting that he greatly changed our execution part: Since we students were not so familiar with the modification part,he not only guided us several ways to modify the bacteriophage, as well as precautions when modifying the bacteriophage.

Furthermore, as for the safety concerns (the phage modification), he said “As long as the experimentation is done in the lab, there will be no concerns. However, if it happens to escape into the environment, since the gene used is not really dangerous, the environmental effect should be low.”

We also consulted him with the E.coli that we would like to do more research on ,( this meeting happened when our experiments were just getting started) , after deep consideration, he replied, “I support you to do so , since E.coli is one of the bacteria that has been doing much research, so it’ll be probably safer. Personally, I also believe that the bacterial envelopes including E.coli could have the potential to boost and improve the protective immunity.”

On the whole, we thank Dr. Chou for guiding us as a prestigious researcher in Virology , and the speech has offered us a lot of confidence with a clear direction of our execution part.

4. Education & Communication

We found the concept of vaccines and viruses are too complicated for children to understand in the street interview ,so we came up with a board game that we then brought on education trips to schools and even to the Science Festival held by National Museum of Natural Science. (Communication informed by silver medal Human Practices)

See more in our "Education" and "Communication" pages.

5. Collaborations & Partnership

Besides improving the world with synthetic biology, Mingdao iGEM has faith that the aim of holding this competition does not stop here. Another critical goal is to connect peers who have a craze for biotech from different ages, races, and identities through interactions with each other, resultingly,we met up with multiple iGEM teams ,including NCHU_Taichung, NCKU_Tainan, CCU_Taiwan, GEMS_Taiwan and so on to execute multiple collaboration projects and even had a long-term partnership with iGEM CSMU Taiwan in this year.

See more in our ”Collaboration” and “Partnership” pages.

6. SDGs & Inclusivity

We aim to fuse the Sustainable Development Goals into iGEM as well as promote the inclusivity of the biotech industry in order to make a contribution to the equality of the world!As for the SDGs, we joined a SDGs’ proposal competition held by the Department of Social Welfare of Taichung City Government, not only interviewed local doctors but also the elderly in our community,in the end, we were rewarded with a special prize. At the same time, we showed our social sensitivity and enlarged iGEM’s inclusivity by focusing on under-resourced children in science and conducted several activities concerned to help those in need.

”See more in our ”SDGs” and “Inclusivity” pages.

Conclusion

Throughout the event, we stuck to our belief of not only doing meaningful activities, but also ensuring that our project can positively impact (our)project purpose, design and execution as well. From the establishment of our project, we did market research to ensure the viability of our project, visited vaccine-developing researchers and virus experts to understand the skills and techniques required to run this industry,

From education and communication, collaborations and partnership, to SDGs and Inclusivity, the HP team has carried out multiple missions that are essential to the whole project. In the end, we would like to show our sincere appreciation to those who have helped with the imperfections, provided pieces of advice, and taught us invaluable know-how along the journey. Our deepest thanks to: Prof. Ming Shiou Jan, Prof.Wen-Wei, Chang, Dr. Nian Ching, Hsiou, Dr. Ren Rong ,Yang, Kien Sung chicken farm, Dongmai pig farm, Tunghai University’s farm, ADIMMUNE Corporation, Prof.Bor Rung ,Ou, Dr. Yu Chi,Chou and many others who provided their precious feedback!