1.
Introduction.
Vaccination is one of the most important measures to prevent
infectious
diseases, and the development of a safe and effective vaccine has become the most urgent task since the
COVID-19 outbreak.
After an exhaustive review of existing data on the efficacy and safety of
various vaccine types,We have developed a COVID-19 recombinant protein vaccine primarily targeting people
of advanced age with underlying diseases (representing 10.3% of the high-risk population in China). This
vaccine offers the advantages of no need for virus exposure and high safety.
However, the technical aspects are just one piece
of the puzzle. To truly create a
project that is both good for and responsible to the world, we must consider a multitude of factors
.
We need to assess the real-world applicability of our project, gauge its
societal impact, understand how societal needs and perceptions could steer our project's direction,
and integrate stakeholder feedback into our development process.
Therefore, we conducted
different
kinds of human practices
activities, as shown below, to answer these questions and
better
design our project. By adopting this holistic approach, we aim to not
only
advance scientific knowledge but also to contribute responsibly to society, ensuring that our
project is not just innovative, but also ethical and socially beneficial
(Figure 1 Flow Chart of Human Practice
s
Activities)
2
Desk research
Before we started HP&IHP designing, we
conducted
the necessary essential reference reading, including
readings that
related to synthetic biology, review-type academic papers, Chinese
vaccine
industry standards, laws and regulations, etc.
The reference to synthetic biology monographs and academic papers
partly
came from the CNKI database, Google Scholar, and recommendations of coaches and researchers in these
related fields as shown in Figure 2.
(Figure 2 Part of reading materials)
The Chinese vaccine standards, laws and regulations documents came
from
our search on government websites, including Law on Vaccine Management of the People's
Republic of
China, Regulations of Vaccine Production and Circulation, Law on the Prevention and Control of
Infectious Diseases of the People's Republic of China, Law on Medicine Management of the People's
Republic of China, Guide to On-Site Inspections of Vaccine Production. Besides, while we were in the process of doing HP, some relevant
companies were also very enthusiastic
about
providing us with relevant legal documents. These documents
gave
us a direct understanding of the current stage of vaccine development requirements and also allowed us
to locate the needs of society from them and provide inspiration for our project.
(Figure 3
Standards, laws, and regulations documents)
We
also
v
isited the World Health Organization (WHO) website about
statistics on
COVID-19. Until 2023 July 9, there were 767,726,861 infected with COVID-19
.
According to Figure 4,
d
espite the end of the global pandemic, new cases and recurrent
infections continue to occur worldwide (WHO, 2020). Therefore, the demand for effective and safe vaccines will
remain
high.
(Figure 4 WHO statistics on COVID-19)
In addition,
t
hrough the desktop research described above, we have analyzed and
organized the current major vaccine R&D pipelines and their comparative status. After studying the ground research, our team has
gained
the background knowledge and start planning about primary research, which led us to the following
Human Practices activities.
(Figure 5 COVID-19 vaccine pipelines)
3
Surveys
The global pandemic of COVID-19 has now ended.
The
relaxation of global disease control policies and such large
data
on infections have made society skeptical about the relevance of vaccinating against n
ovel
coronaviruses. Nevertheless, antibody titers in the body
(both
vaccine- and infection-generated) decline over time. Concurrently, the long-term trajectory of COVID-19 distribution
poses a
significant risk of multiple infections, thereby jeopardizing overall public health. In light of this,
it is advisable for everyone to receive booster shots as a preventive measure against potential health
risks. Therefore, two online questionnaires were conducted to find out
the
current status of
COVID-19 infecti
on
and
previous vaccination in the population, and public awareness
and
willingness to vaccinate against COVID-19.
3.1 Questionnaire 1
Characteristics of the questionnaire on the status of
COVID-19 infecti
on and previous vaccination
Through an online survey based on a Microsoft online form, we
collected
211 questionnaires. Overall, there was a high prevalence of COVID-19 infections, which were relatively
concentrated, with respiratory symptoms predominating, infections that caused some participants to have
direct or indirect economic losses, and even life-threatening infections in some of their participating
relatives and friends.
(Figure 6 main
results
of o
nline
survey
1)
Important results of the first questionnaire
1. Although less than one in ten participants had not been infected,
a
non-negligible proportion of those who had been infected were repeat
ed
over a short period of time.
2
. The vast majority of infections are now characterized by
relatively mild
respiratory symptoms.
3
. Less than half of the participants' lives were unaffected, while
the
others were more or less impaired in various ways.
4
. The
incidence
of life-threatening
complications
due to infections
can
not be ignored. .
3.2 Questionnaire 2
Characteristics of the questionnaire on public awareness and
willingness
to vaccination
In the second questionnaire, the overwhelming majority of respondents had
completed the full basic vaccination regimen. However, a significant portion of participants
demonstrated a lack of knowledge about the vaccine and exhibited limited willingness to receive
future vaccinations. 
(Figure 7 main
results
of o
nline
survey
2)
Important results of the second questionnaire
1. A
lthough
m
ore than 80
%
of participants have completed the full course of basic
vaccines
, only 1% received booster shots.
2
. Nearly half of the participants did not know the specific type of
vaccine they received.
3
. All types of vaccines were heard of by 10 to 20
%
of
respondent
s.
4
. The vast majority of participants were uncertain about whether
they
would continue to receive booster shots.
Reflections
COVID-19 vaccination helps the body to produce "neutralizing
antibodies"
against the virus, but over time the amount of vaccine-induced neutralizing antibodies slowly decreases,
and the neutralizing effect on the virus is weakened, which may lead to a decrease in the protective
effect of the vaccine. Despite a global decline in the level of attention
given
to COVID-19 compared to previous years, our survey has identified a concerning trend toward
re-infection.
Specifically, individuals who were infected more than six months ago did
not maintain effective antibody levels through vaccination, leaving them vulnerable to re-infection
Given the
waning societal emphasis on vaccination
, it is
crucial
to
engage in community education to raise awareness about the
significance of vaccination and to
promote the availability
of
safe and effective vaccines
.
(Click
here
to check the Education)
4
I
nteraction
with
corporations and
experts
Vaccine research and development has strict industry norms and
legal and
policy requirements, with clear regulations on various aspects such as environment and ethics. At the
same time, the higher costs and technological complexity of R&D and production affect our research
design. Therefore, we visited a COVID-19 vaccine R&D company and had a one-on-one conversation with the
head researcher of the company to address the technical and economic concerns of the vaccine R&D and
production process. We also visited the R&D laboratory of the enterprise.
4.1
Visit Zeotis
Zoetis is one of the largest companies in the global animal health
pharmaceuticals and vaccines industry and
was
the animal health division of Pfizer. Currently, Zoetis
focuses on
services for the prevention, control, treatment, and rehabilitation of animal diseases, and a
recombinant subunit vaccine for coronaviruses is one of the main product pipelines currently under
development by this company.
After visiting Z
oetis
' research laboratory, we interviewed Dr
.
Liu of the company. Dr
.
Liu is the senior researcher of vaccine development of
Z
oetis
, and he has rich experience in the development of swine fever
avian
influenza vaccine and coronavirus recombinant protein vaccine for animals. We had a relaxed but
informative conversation with Dr. Liu about vaccine development costs, research competition, technical
difficulties, and pain points, as well as vaccine marketing.
(Figure 8
L
aboratory
visit
)
Dr
.
Liu briefly introduced us to the domestic and international
market
situation, safety and efficacy testing issues for vaccine development and marketing, vaccine promotion,
and future technological advances in recombinant protein vaccines.
(Figure 9
I
nterview
of
D
r.
L
iu
)
Through
this
interview
, we received some reflections which influenced our project in many ways
:
(1) As far as the Chinese market is concerned, the market demand for
vaccines is high.
(2) Different strategies should be considered in the promotion and
marketing
of vaccines. For example, different strategies need to be developed for
end-users
, sales scenarios, etc. to promote awareness among different
populations
or organizations.
(3)
The potency of recombinant vaccines can be augmented through advancements
in structural biology. Utilizing techniques from this field allows for the examination of viral
protein structures and the identification of potential immunogenic sites. This enables the selection
of sites with superior antigenic properties for vaccine design
.
4.2
Expert interview
Professor Zhenggang
Han
Prof. Han is a pharmacologist and pharmacy scientist from Wuhan
Polytechnic University
, who has long focused on researching how to develop highly
effective
new drugs using synthetic biology techniques. Through our interviews, we learned that although the
global pandemic of COVID-19 has now ended, the situation is still serious in terms of dissemination and
localized micro-epidemics across the country and around the world. Therefore, the risk of re-infection
continues to increase as antibodies decline over time, and vaccination is the safest way for us to
acquire new antibodies.
(Figure 10
I
nterview
of
P
rofessor
H
an
)
According to Professor Han, r
ecombinant protein vaccine technology itself is already relatively
mature. In China, a large part of the development of hepatitis B vaccines is based on recombinant
protein technology and has been widely used in China. Therefore, the safety of recombinant protein
vaccine technology has been tested. In contrast, the newer mRNA technology is the first time it has been
used in humans, so its safety is not yet known. Meanwhile, the safety and efficacy of the more widely
used inactivated vaccines
are
dwarfed by that of recombinant protein vaccines. Finally, in terms of national policy, there are no additional
supportive
policies to promote vaccine development and production in China at this time due to the well-known
termination of the COVID-19 pandemic, but similarly, there are no additional restrictions or
regulations.
Major r
eflections:
a: Recombinant protein vaccine technology is well established and
safety
is guaranteed, but there are limits to its effectiveness.
b
: The more advanced and well-studied mRNA vaccines are currently
available globally, but their efficacy and safety are unknown. Therefore, recombinant protein vaccines,
which may be less effective but safer, are the preferred choice for current research and the
market.
c: Currently, neither the market nor policies are particularly
favorable
but at the same time not restrictive for COVID-19 vaccines, so no special preparations are needed for
the design and development of vaccines, but only for the safety of the current national requirements for
drug development.
Professor
Yibei
Xiao
Prof. Xiao is an expert from the Department of Pharmacology, China
Pharmaceutical
University, and has long focused on the molecular mechanism
of
action of gene editing tools and their applications, drug target discovery and validation, and the
confrontational
relationship of drug/target interactions.
(Figure 11
I
nterview
of
P
rofessor
X
iao)
Similar to Prof. Han, Prof. Xiao also compared the current
inactivated
vaccines, recombinant protein vaccines, and mRNA vaccines, which are the most common vaccines in the
world, from various aspects of recombinant protein vaccine technology. The difference is that Prof. Xiao
believes that the mRNA vaccine is the most effective vaccine at present. This is because the recombinant
protein vaccine itself is a subunit vaccine and its protein has a smaller molecular weight. The body
reacts differently to the size of the immune material, and for the larger mRNA, the smaller size of the
subunit itself is less effective in being recognized and processed by the body and making a
response. Therefore, Prof. Xiao suggested ways that could be improved at
present,
such as constructing multimers. This will not only achieve immunization against multiple viral variants
simultaneously
but also better stimulate the body to respond and produce
antibodies.
Major r
eflections:
a: Recombinant subunit vaccines can be significantly less
effective than
mRNA vaccines due to their inherent design flaws, which are caused by the lower immunogenicity of the
subunit vaccine itself.
b
: The construction of vaccine proteins with multiple potencies is
a
question worth pondering if the protective effect of vaccines is to be strengthened.
c: Protein vaccines have a small molecular structure and poor
immunogenicity, so constructing protein vaccines that are more efficient in stimulating the body to
produce an immune response is a research direction that needs to be worked on, when the safety of mRNA
vaccines has not been clinically tested.
4.3
Business Plan Roadshow
After an initial understanding of the vaccine and its role through
questionnaires and interviews, we conducted an initial business analysis of our product and wrote a
business plan. We presented our business plan to professional business investors. We showed Mr.
Zhongtian
Ye our business plan, which mainly includes the results of the
PESTLE
analysis,
SWOT
analysis, and 4P analysis. After this, we also interviewed
Mr.
Y
e
on cost planning, merchandising, and publicity
design.
(Mr. Zhongtian Ye is a Chartered Quantitative Financial Analyst (CQF) and
Senior Manager in Investment Banking with extensive experience in industry research and analysis. He
has previously served in strategy roles at Fortune 500 companies, specializing in digital
transformation and AI applications. Mr. Ye has been deeply involved in IPO underwriting, including
projects on the Shenzhen and Beijing Stock Exchanges. His investment portfolio spans multiple
sectors and countries, from a sensor company in Germany to a petrochemical investment in Africa
)
(Figure 12
Business Plan
P
itch)
Mr. Y
e
provided some important advice on our business plan
(Click
here
to check the Entrepreneurship)
:
(1) With vaccine safety in the news and the general public already
infected, it is critical to disseminate the product and educate.
(2) Currently, the Chinese market for vaccine products is
relatively
restricted, and the impact of the unified procurement of health insurance on various aspects such as
price makes the products lack more freedom.
(3) Products should be positioned with different designs and
target
groups, targeting the general public should provide low-priced safe, and effective products, while
targeting other high-income groups should highlight newer technologies and more effective but more
expensive products.
(4) Presenting a good market logic that demonstrates the
advantages over
similar goods is significant for
promoting
a new product. That is, what is needed to energize the
market is a
product story logic, based on developing the product's own value.
5.
Conclusion
(1) Although COVID-19 infections are widespread, population
immunity
declines over time, making vaccination the safest way for populations to maintain antibodies to avoid
re-infection. This underscores the critical role of vaccination
as the
most reliable method for populations to sustain antibody levels and prevent re-infection. Our
project aims to address this by focusing on the development of a COVID-19 recombinant protein
vaccine.
(2) The public is not aware of the different types of vaccines and
their
safety and efficacy,
To bridge this knowledge gap, we desgined and implemented targeted
educational campaigns that aim to rationalize and promote health-conscious behaviors among the
public.
(3) Vaccination with COVID-19 recombinant protein vaccine is a
relatively
safer and effective strategy, but due to its small molecular weight, it is less immunogenic therefore
designing more multivalent multimeric heavy histones is important to improve the immune
performance.
(4) Both merchandising and health education require different
strategies
designed to target different populations. At the same time, telling the product's story
logically
is an extremely
crucial
thing. Therefore, crafting a compelling narrative for our
product is paramount. Through our human practices, we've gathered valuable insights and stakeholder
feedback that will inform both our marketing and educational outreach strategies.
We have developed a COVID-19 recombinant protein vaccine primarily targeting people of advanced age with underlying diseases, representing 10.3% of the high-risk population in China.
We envision others using our project by considering neutralizing antibodies, such as our monoclonal antibody product, as a key strategy for the effective prevention and treatment of the new coronavirus. This approach offers a clear mechanism of action and easy mass production and is an important direction for the research of preventive and therapeutic drugs. This vaccine offers the advantages of no need for virus exposure and high safety.
We'll implement our project by educating the public through outreach efforts, collaborating with organizations, and promoting recombinant protein vaccines via informative posters in hospitals and other community sites. We'll seek support and advice from experts and authorities, with financing details to be determined.
6.
Reference List
WHO COVID-19 Dashboard. Geneva: World Health Organization, 2020.
Available online: https://covid19.who.int/ (last cited: 2023 July 9).
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