Business Plan: Broad-spectrum influenza vaccine based on the HA2 region

1.Project Positioning

1.1 Project Introduction

Our project team is developing a novel broad-spectrum influenza vaccine that will protect against multiple influenza virus subtypes and provide a more durable immune response. We have discovered that influenza viruses primarily infect human cells through the HA region, but the HA1 region, targeted by common vaccines, is prone to mutation. In contrast, the HA2 region of the virus is less susceptible to change. Therefore, by injecting our vaccine targeting the HA2 region, we can induce the body to produce antibodies against HA2, thereby achieving a longer-lasting and broader immune response.

Intention

Protecting people's health and achieving wider influenza immunity.

2.Market Research

2.1 Industry Overview

2.1.1 High Demand for Public Health

With population growth, accelerated urbanization, and increased global mobility, the speed and scope of infectious diseases have significantly increased, and the demand for influenza vaccines is also growing. According to data from the World Health Organization (WHO), the number of people testing positive for influenza is on the rise each year. Approximately 2 million people die annually from vaccine-preventable diseases (such as pneumonia, influenza, and HPV-related cancers), 30% of whom are children under the age of 5 (WHO Global Vaccine Action Plan 2023). According to the United Nations database, the proportion of the global population aged 65 and over is expected to increase from 9% in 2020 to 16% by 2050. These individuals are at high risk for influenza and should be fully vaccinated.

In summary, the prevalence of influenza will continue to rise in the coming years, and the market for influenza vaccines will therefore grow, driving sales.

2.1.2 High Cost of Existing Vaccines

Given the high development and production costs of current seasonal influenza vaccines, some people in middle- and low-income groups and low-income groups cannot afford effective immunization.

Table 1: 2025 List of Winning Bids for Influenza Vaccines (Publicly Funded Vaccines) under Immunization Programs

Supplier	Product Name	Specifications	Quantity (Dose)	Unit Price (10, $)	Total Price (10, $)
Hualan Biology	Trivalent Influenza Vaccine	0.5 ml / 15 μg per dose	420000	0.001	420
Shanghai Institute	Trivalent Influenza Vaccine	0.5 ml / 15 μg per dose	630000	0.00055	346.5
Beijing Kexing Bio	Influenza Split Vaccine	0.5ml/15 μg per dose (Note: This is calculated)	-	6.3	630

2.1.3 The Vaccine is Not Yet Mature

mRNA Influenza Vaccine Effectiveness is Inconsistent

In terms of efficacy against influenza type II viruses, mRNA-1010's serum conversion rate and average geometric antibody titers against types II Victoria and Yamagata viruses fell short of expectations. Furthermore, it also had a higher incidence of adverse reactions, with a reported adverse reaction rate of 70%, compared to 48% for the control inactivated vaccine, Fluarix Tetra.

Unstable Efficacy (Seasonal Influenza Vaccines)

Seasonal influenza vaccines include inactivated, live attenuated, and recombinant types:

• Inactivated vaccines account for 98% of the global supply and are primarily produced in eggs or cell cultures. Their annual protection rate is only 20% to 60% and is significantly affected by viral mutations. When the recommended vaccine strain does not match the circulating strain, efficacy can plummet.
• Live attenuated vaccines are not suitable for immunocompromised individuals.
• Recombinant vaccines are costly and limited in supply.

2.1.4 Questionnaire

We received approximately 300 questionnaires. Analysis of the two charts below shows that the majority of people around us have not been vaccinated for various reasons, highlighting the inadequacy of existing vaccines. Furthermore, regarding the newly developed broad-spectrum vaccine, 75 respondents expressed a willingness to actively receive it, while over 150 chose to wait for the vaccine's effectiveness and maturity. This suggests that as long as vaccine quality is guaranteed and production is efficient, vaccination rates will be extremely high. These feedbacks show that people are willing to try new vaccines, which gives our project a very good development prospect.

2.2 Market Analysis

2.2.1 The Demand for Products is Increasing

According to a seasonal influenza vaccine market analysis released by the World Health Organization, global demand for seasonal influenza vaccines is expected to increase by at least 10% between 2024 and 2034, from 850 million doses to 920 million doses. Considering that broad-spectrum vaccines do not require seasonal purchases, they are likely to attract purchases from lower- and middle-income countries. Therefore, the market for broad-spectrum influenza vaccines is expected to be even larger than that for seasonal influenza vaccines.

Historical and forecast data (Base case): 2019 (400 million doses), 2020 (573 million doses), 2021 (844 million doses), 2023 (848 million doses), 2028 (870 million doses)

2.2.2 Market Size

As shown in Figure 5, from 2019 to 2025, the market size of China's influenza vaccine industry has generally been on the rise.

Figure 5: China Quadrivalent Influenza Vaccine Market Size, 2017-2030E (Unit: Billion CNY)

Production Value & CAGR:

• 2017: 10.7; 2018: 42.9; 2019: 59.9; 2020: 86.4; 2021: 107.8; 2022E: 133.2; 2023E: 160.8; 2024E: 195.0; 2025E: 226.3; 2026E: 253.8; 2027E: 283.9; 2029E: 317.4; 2030E: -
• CAGR: 2018-2021 (109.0%), 2021-2025E (24.0%), 2025E-2030E (-)

From 2017 to 2022, the global vaccine market revenue showed an upward trend as in Figure 6. The chart predicts that the vaccine market size will further expand by 2027.

2.2.3 Policy Support

In 2019, the World Health Organization launched the "Global Influenza Strategy 2019-2030," encouraging countries worldwide to strengthen their preparedness and response capabilities for influenza, thereby reducing the burden of seasonal influenza and the impact of pandemic influenza. In response to this strategy, China launched the "Healthy China Action (2019-2030)" initiative, encouraging free influenza vaccinations for people aged 60 and over, children in childcare institutions, and students in primary and secondary schools, as well as vocational secondary schools, across all regions of the country.

3.Product introduction

3.1 Core Technology

Core Technology

Our projects primarily revolve around recombinant protein technology. Leveraging a sophisticated recombinant protein expression system, we precisely express highly conserved epitopes found in influenza viruses—epitopes that rarely change with mutation, thus providing long-lasting immunity.

Essential Technology

We transcend the limitations of traditional vaccines, which target specific strains. By targeting conserved antigens, we activate the body's cross-immune response to multiple strains, achieving broad-spectrum protection across subtypes and over a long period of time, addressing the root causes of the prevention and control challenges posed by viral mutations.

3.2 Competitive Analysis

Product Features

• Conserved antigen screening: Utilizing computer analysis techniques to precisely locate antigens that possess both immunogenicity and cross-species conservation properties.
• High immunogenicity: Utilizing ferritin (iron protein) as a carrier to enhance the immunogenicity of the vaccine.
• Low risk of mutation escape: Targeting highly conserved antigenic regions to prevent immune failure caused by viral mutations.
• Wide range of immunity: Targeting antigenic epitopes across different strains to achieve immunity against multiple strains.
• Low risk of side effects: Without any viral structure or genes, it reduces the risk of adverse reactions in the human body.

Our Vaccine vs Existing Vaccines

Vaccine Types	Split Vaccine	Whole Virus Inactivated Vaccine	Recombinant Protein Vaccine	Our Vaccine
Vaccine Components	Surface antigen, internal antigen	Surface antigen, internal antigen, reactogenic lipids	Protein antigen	Protein antigen
Immunogenicity	Strong	Strong	Weak	Weak
Side Effect	Low	High	Low	Low
Immunization Range	Single-strain	Single-strain	Single-strain	Multiple-strain

4.Risk Assessment

4.1 Technological Updates and Iterations

The current vaccine technology is evolving rapidly, with numerous new vaccine technologies constantly being developed. Although our project has unique advantages, if during the research and development period, more advanced and efficient influenza vaccine technologies emerge that can better address the shortcomings of existing vaccines, our project may lose its competitiveness, resulting in a decrease in the market value of the research and development outcomes.

4.2 Market Acceptance

Although the questionnaire survey indicates a relatively high vaccination rate, in actual market promotion, there is still uncertainty regarding consumers' acceptance of the new vaccine.

• On one hand, some consumers may have doubts about the safety and efficacy of the new vaccine, especially when there is a lack of long-term clinical data support, which may cause hesitation and affect the market penetration rate of the vaccine.
• On the other hand, the existing flu vaccine brands have already established a certain user base and brand recognition in the market. The new vaccine entering the market requires a significant investment in promotion.

5.Business Model

5.1 Business Model

Our team conducts vaccine research and development, and in the future, this outcome can be further developed by university laboratories or pharmaceutical companies, while we outline a feasible commercialization pathway.

Patent Licensing

Guaranteeing production through collaboration with businesses. Some manufacturers prefer to conduct their own R&D. We can provide technical support during their R&D process. If their experiments encounter any issues, we can offer technical assistance and collaborate with them to complete R&D, ultimately achieving a mutually beneficial outcome.

5.2 Expectancy

We are exploring whether this scientific outcome could potentially be applied in the future by using an entrepreneurial mindset.

6.Evaluation

1. 6.1 Government
   The government is concerned about how to reduce the incidence and mortality of influenza, and how to reduce the damage of influenza to the public health system, so this program can effectively provide assistance to the government.
2. 6.2 Doctor
   Doctors need to recommend vaccines with high protection rates and low side effects to patients to avoid medical accidents caused by poor vaccine effectiveness or adverse reactions.
3. 6.3 Student
   Students are afraid of the pain of vaccination or worry that discomfort after vaccination will affect their studies and extracurricular activities.
4. 6.4 Pharmaceutical companies
   Pharmaceutical companies are concerned about low market acceptance of new vaccines and fierce competition, while also facing policy risks.

7.Laws and Regulations

7.1 Approval Process

Key Compliance Steps for New Vaccine Development at Home and Abroad

China

1. a.Preclinical research: Strain screening, attenuation, etc. are conducted to test process stability and animal experiments.
2. b.Clinical application filing: Multi-disciplinary research data are submitted. After approval, a clinical approval document is obtained.
3. c.Institution application: Apply for the recognition of the testing institution and obtain the corresponding approval document.
4. d.Registered clinical trials: Human trials are conducted in phases I-III to evaluate safety and efficacy.
5. e.Subsequently: After approval for production and marketing, phase IV monitoring is required. The clinical period lasts at least 3-8 years, and strict supervision is implemented.

European Union

1. a.Clinical Trials: Through Phase I/II/III trials, safety, dosage, and efficacy are successively evaluated. Phase III requires several thousand to tens of thousands of cases for confirmation.
2. b.Intellectual Property Protection: An 8-year data protection period, with transferable exclusive rights certificates and other measures to safeguard the rights and supply of pharmaceutical companies.
3. c.Regulatory Approval: Submit complete materials to the EU Medicines Agency. Only after the review is qualified can it proceed to clinical trials.
4. d.Production and Supply: The holder guarantees production capacity. In case of shortages, member states can require enterprises to provide additional supplies.

America

1. a.Clinical trial: Divided into three phases, it successively verifies safety, effectiveness, dosage, protective efficacy and long-term safety.
2. b.Regulatory assessment: The FDA reviews the production process, trial data, and side effects to confirm safety and effectiveness.
3. c.Production control: With FDA approval, production complies with GMP standards and undergoes regular inspections.
4. d.Market approval: Reviewed and approved by the ACIP and CDC directors, it is included in the national immunization program.
5. e.Post-market monitoring: Through the VAERS system, adverse reactions are tracked and reported to the regulatory authorities in a timely manner.

7.2 Related Regulations

Application Channels

China

1. a.Clinical trial application: Submitted through the national drug administration portal, complete the required documents in accordance with the ECTD format, undergo form review, and if termination is required, a new application must be submitted.
2. b.Marketing authorization application: Submitted to the drug review center, prepare the required documents in accordance with relevant regulations, undergo review, evaluation, and approval, and meet the requirements of the "Vaccine Administration Law".
3. c.Special vaccines:
• Immunization program vaccines emphasize full life-cycle management and free vaccination;
• Non-immunization program vaccines follow a similar process, with the cost being self-funded. All must comply with the latest regulations.

International

1. a.BLA application in the US: Submitted to the FDA, it requires verification of production process consistency, provision of key Phase III clinical data, and may need to supplement data. The review period may be extended.
2. b.Cross-border transportation: Requires obtaining the "Special Items Health Quarantine Approval Form for Entry and Exit of the Country", which involves qualification filing, submission of materials, and port inspection. It can be processed through a single window. (Note: There are differences in requirements among countries. It is necessary to confirm with the target market.)

7.3 Expert Consultation

Since the market may question our effectiveness, we sought out experts for interviews and learned relevant information about the vaccine market. Based on this interview, our iGEM team gained crucial insights that have directly influenced both the direction and methodology of our vaccine project. Professor Deng's expertise highlighted the complex nature of influenza virus variability and the challenges this poses for broad-spectrum vaccine development. We learned that while targeting conserved regions such as the HA2 stem is theoretically promising for universal protection, its poor exposure to the viral surface often results in weak immune responses. This has encouraged us to adopt strategies that enhance immunogenicity, such as leveraging ferritin nanocages as antigen display platforms—an approach Professor Deng noted is already advancing in clinical trials. Additionally, the discussion emphasized the limitations of current validation models and the importance of practical alternatives.

Based on this interview, we have integrated Professor Deng's advice throughout our DBTL cycle. In the Design phase, her insights on immunogenicity guided us to use AI and structural biology to select more exposed epitopes. For the Build phase, her support of ferritin nanocages led us to choose ferritin as our antigen display scaffold.

We have designed a potential commercialization pathway that can be carried forward by research institutions or industry in the future. Our goal is to demonstrate that a high school team can also use scientific and entrepreneurial thinking to address public health challenges.

8.SWOT Analysis

Strengths	Weaknesses
Innovative: Targets conserved HA2 region for broad, long-lasting immunity. Reduced mutation escape risk compared to current vaccines. Fewer side effects; no viral genetic material. Surveyed market shows openness to new vaccines. Aligns with public health policy and needs.	Lack of long-term clinical efficacy/safety data. May face slow market penetration against established brands. High cost & time for development and approval. Potentially suboptimal immune response without advanced scaffolds. Many consumers want to wait for more evidence before acceptance.
Opportunities	Threats
Rising global flu vaccine demand and aging population. Strong government and policy support for vaccination. Potential to serve emerging markets with fewer seasonal resources. Technology licensing and B2B partnerships. Advances in AI and structural biology can optimize product further.	Rapid advances in competing vaccine technologies (e.g., mRNA, others). Complex, lengthy regulatory processes and differences between countries. Public and physician hesitancy without brand recognition or data. IP risks and supply chain scalability challenges. Existing entrenched vaccine brands and market loyalty.