Watson Biologics and Huang Zhen: The Rise of mRNA Vaccines and the Critical Need for Chemically Defined, Mechanistically Understood Culture Media

The COVID-19 pandemic has been a major watershed moment for the development of China’s vaccine industry.

Since the COVID-19 pandemic, China has rapidly advanced from traditional vaccines to emerging vaccine technologies. The race to develop COVID-19 vaccines propelled mRNA vaccines to prominence as star products, fostering a diverse landscape of technological innovation. Novel vaccine platforms, including recombinant protein vaccines and adenovirus-vectored vaccines, have experienced robust growth.

Amid the surge of novel vaccine technologies, the industry has gained a deeper understanding of supply chain system development, and the strategic importance of critical raw materials, such as culture media, has received further attention.

Walvax is the domestic company with the largest number of marketed vaccine products under single ownership, and it is the only enterprise in China that simultaneously holds two of the world’s best-selling vaccine products (HPV vaccine and 13-valent pneumococcal conjugate vaccine). Meanwhile, through a combination of independent R&D and collaborative development, the company has established emerging technology platforms such as mRNA vaccines and adenovirus-vector vaccines, positioning itself at the forefront of vaccine technological innovation.

Huang Zhen, Vice Chairman of the Board, has been deeply engaged in the field of biological products for over 40 years. He possesses extensive experience in vaccine research and development (R&D) and production management, demonstrating first-class technical expertise in the R&D of bacterial polysaccharide vaccines and bacterial polysaccharide conjugate vaccines. Huang Zhen stated, “Chinese vaccine enterprises are currently in a phase of catching up and are on the verge of entering a phase of running alongside global leaders. In the next three to five years, a cohort of Chinese companies will emerge to stand shoulder-to-shoulder with leading overseas vaccine manufacturers, and I believe Walvax will be among them.”

What reflections has the COVID-19 pandemic prompted within the industry? How will the vaccine supply chain system evolve in the post-pandemic era? What role do culture media play in the industrial chain? Recently, VBInsight, in collaboration with Thermo Fisher Scientific, conducted an exclusive interview with Huang Zhen, Vice Chairman of Walvax Biotechnology.

Walvax has launched eight vaccine products, including two globally significant blockbuster vaccines: the 13-valent pneumococcal conjugate vaccine and the HPV vaccine.

Among these, the 13-valent pneumococcal conjugate vaccine was Walvax’s most challenging project. The manufacturing process for the 13-valent pneumococcal conjugate vaccine is complex, and many multinational corporations have previously failed in their attempts. In particular, during the R&D period, the approval of patents for imported products in China posed further difficulties to the development efforts. Walvax modified and revised the protein carrier, adoptingTechnical Route for the Conjugation of Tetanus Toxoid with Pneumococcal Capsular Polysaccharides, successfully becomingThe world’s first, and to date the only, 13-valent pneumococcal conjugate vaccine that fully utilizes this carrier and has been successfully developed and launched on the market.

Since its inception, humanity has been engaged in a struggle against various pathogens and viruses in nature. Viruses and bacteria have served as the primary drivers of progress in the vaccine industry, and Walvax Biotechnology experienced a significant turning point following the outbreak of the COVID-19 pandemic. In the first half of 2020, amid the severe epidemic situation, Walvax Biotechnology transitioned from traditional vaccines to new-generation vaccine technology platforms.

VBInsight: Walvax built its foundation on bacterial vaccine platform technologies. Why did the company rapidly decide to deploy innovative vaccine technologies, such as mRNA vaccines, after the outbreak of the COVID-19 pandemic?

Huang Zhen:At that time, the company engaged in intense internal debate over whether to develop traditional vaccines for rapid emergency use or to leverage this opportunity to establish a presence in emerging technological pathways. Based on our strong conviction in technologies such as mRNA, we chose a more challenging path with greater potential for innovation and growth.

Walvax and Abogen have collaborated to establish a strategic presence inmRNA Vaccine Technology Platform, China’s first mRNA vaccine for the novel coronavirus has completed Phase III clinical trials; leveraging the layout of Shanghai ZerunRecombinant Protein-Based COVID-19 Vaccine Platform,Offers the advantages of easily scalable production capacity, high stability, and high safety; collaborates with Tsinghua University to strategically positionAdenoviral Vector Vaccine Platform。

The correctness of Walvax’s initial strategic choices has been validated, as mRNA vaccines, recombinant protein vaccines, and adenovirus vector vaccines have all garnered significant attention and recognition within the biopharmaceutical industry. Notably, adenovirus vectors have achieved breakthroughs in mucosal immunization therapies, presenting substantial opportunities for future development. Leveraging the characteristics of mucosal immunity in combination with IgG and IgA antibodies promises to be a transformative approach, opening new avenues for the prevention of COVID-19.

VBInsight: What position will new vaccine technologies, such as mRNA, occupy in the future vaccine industry? Will they have a significant impact on the traditional vaccine industry?

Huang Zhen:This is certain; mRNA vaccines can be regarded as the “discovery of the steam engine during the Industrial Revolution,” and will undoubtedly bring about revolutionary changes.

The United States began developing mRNA vaccines in the late 1960s and early 1970s, but made no significant progress for decades. The COVID-19 pandemic was a disaster, yet it also spurred major technological breakthroughs.Without the COVID-19 pandemic, the widespread application of mRNA technology in the vaccine field might have taken another 10–20 years.It was the pandemic that rapidly propelled mRNA technology to the forefront.

VCBeat New Medicine: What Insights Did the COVID-19 Pandemic Bring to the Industry, and Why Does Walvax Place Such High Importance on Building a Vaccine Technology Platform?

Huang Zhen:The mutation of pathogenic microorganisms is the core driver of significant transformation in the industry. The COVID-19 pandemic has taught us not to fight unprepared battles. In our defense against COVID-19, we have been playing catch-up with the virus; however, there will come a day when we stay ahead of it and ultimately eradicate it.

To achieve this goal, it is essential to establish robust emergency response and protective measures against pathogenic microorganisms, along with developing platform technologies. With such platforms in place, whenever a novel infectious disease emerges, a new vaccine can be developed within 60 days as long as the effective gene sequence responsible for the disease is identified—a feat that would be unimaginable under traditional vaccine development systems. Without platform technologies, we would remain perpetually passive and powerless.

In the future, the vaccine sector will be dominated by two major technological platforms: mRNA platforms and polysaccharide-protein conjugate technologies.

First, the antigens in vaccines such as recombinant protein vaccines and genetically engineered vaccines are protein-based; these technologies can all be replaced by mRNA technology. We are highly optimistic about the prospects of mRNA technology in the prevention of major diseases, including HIV/AIDS and gastric cancer.

Additionally, bacteria possess the ability to self-replicate. Their antigenic components are polysaccharide antigens located on the cell wall. Due to their simple antigenic structure, unlike proteins with complex spatial configurations, mRNA technology cannot effectively address bacterial infections, necessitating reliance on polysaccharide extraction. However, as polysaccharides are haptens, they elicit a poor immune response in children under five years of age. The emergence of polysaccharide-protein conjugation technology has resolved this issue.

VBInsight: What is your forecast for the overall development trend of China's vaccine industry?

Huang Zhen:China has long advocated the policy of “prevention first, treatment second,” and is one of the few countries worldwide capable of meeting its infectious disease prevention needs through domestic manufacturing capacity.

Bullish on the role and status of Chinese vaccine enterprises in the international arena.Chinese vaccine companies are poised to shine, particularly in Belt and Road Initiative countries. To strengthen their global footprint, these enterprises must prioritize PQ certification and localized production. Walvax has already exported its vaccine products to 15 overseas countries and recently established a partnership with MarocVax in Morocco, successfully exporting the first batch of one million doses of its 13-valent pneumococcal conjugate vaccine to the country. Moving forward, Walvax will initiate local production in Morocco, leveraging it as a hub to serve the entire African continent.

Following the Changchun vaccine incident, escalating regulatory requirements and companies’ own development needs have spurred vaccine manufacturers to accelerate innovation. The promulgation and implementation of the Vaccine Administration Law in 2019 further mandated regulatory compliance and encouraged innovation in vaccine research, development, and production, paving the way for the emergence of globally competitive Chinese vaccine enterprises.

mRNA vaccines represent a disruptive innovation in the field of vaccinology, imposing higher and more urgent demands for supply chain upgrades.

Traditional vaccine companies operated in silos, able to complete vaccine R&D and production simply by purchasing raw materials. mRNA technology entails higher standards and greater development complexity, making it unrealistic for companies to attempt a fully vertically integrated “end-to-end” approach. Instead, stakeholders must collaborate across all stages of R&D and manufacturing, with extensive cooperation in areas such as plasmids, consumables, and chromatography resins. This collaborative model represents the ideal paradigm for novel vaccine development.

In particular, the stability and high quality of culture media in the supply chain are critical.Cell culture media are an indispensable and critically important raw material for vaccine production. Huang Zhen first encountered Thermo Fisher Scientific’s Gibco cell culture media while working at the Chengdu Institute of Biological Products, and he has long been impressed by Gibco’s outstanding performance in cell culture applications. “Gibco cell culture media offer multiple advantages, including high quality, high efficiency, and high stability, providing effective support for vaccine development.”

To date, Walvax has collaborated with Gibco for many years, and Gibco has witnessed the birth of multiple blockbuster products from Walvax.

VCBeat New Medicine: What Does Culture Media Mean to the Vaccine Industry in Its Development Process?

Huang Zhen:Culture media are classified into bacterial culture media and viral culture media.

Bacterial culture media are relatively straightforward; the challenge lies in viral culture media. As is well known, viruses require a vector or host for replication, DNA transcription, and protein translation. Since viruses propagate through cells, cell culture media become crucial.

To develop optimal cell culture media, it is essential to study the growth patterns and genetic characteristics of the cells themselves. High-quality culture media can facilitate cell proliferation, thereby benefiting viral replication. Without high-quality culture media, ideal cell culture and viral replication cannot be achieved, let alone the development of superior vaccines.

VCBeat New Medicine: What New Requirements Do mRNA Vaccines Pose for Cell Culture Media?

Huang Zhen:Amid the mRNA vaccine boom, orders for cell culture media have surged, enabling many manufacturers to achieve rapid growth. However, the development and selection of culture media often rely on empirical experience, with a limited understanding of the underlying mechanisms.

Vaccines are administered to healthy populations, imposing stringent requirements on cell culture media. There is a critical need for media with well-defined functional characteristics, adhering to the principle of “understanding both the phenomenon and its underlying mechanism.” It is not sufficient merely to support robust viral replication; the mechanistic basis must also be fully elucidated. This presents a significant challenge, as well as a major opportunity, for culture media development. In the future, the industry will undoubtedly favor culture media with clearly defined conditions, components, and mechanisms of action.

Currently, the mechanisms of culture media utilizing animal-derived products are not yet fully elucidated, posing a risk of viral contamination to cells.Future vaccine development will undoubtedly require culture media with well-defined mechanisms and compositions, and the selection of raw materials for these media will shift from animal-derived products to animal-free alternatives., during its collaboration with U.S. enterprises, Walvax was explicitly informed that all raw and auxiliary materials must be free of animal-derived components. This transition will eliminate a large number of companies.

Arterial Network New Medicine: Why Choose Gibco as a Partner in Culture Medium Selection? What Are the Key Considerations?

Huang Zhen:Walvax’s original aspiration is to become a trusted global vaccine supplier, which requires both Walvax’s internal capabilities and the external support of its partners, working in sync and resonance.

Most of Walvax’s partners are leading overseas enterprises. For the vaccine industry, integrity, quality, and safety are the lifelines. When selecting suppliers, Walvax first considers whether the supplier’s pursuits and culture align with its own philosophy. Secondly, both the enterprise and its products require the test of time. With a 60-year development history, Gibco is a global leader in cell culture media, boasting profound expertise. Its product quality and safety have been validated over time, making it a choice that Walvax wholeheartedly embraces.

Artery New Medicine: Do you believe that China's vaccine industry has already established a comprehensive and robust supply chain system? Where do future opportunities lie?

Huang Zhen:Overall, China’s supply chain system remains insufficiently robust. Prior to the enactment of the Vaccine Administration Law, companies managed their supply chains in a relatively ad hoc manner, often prioritizing cost considerations. Following the implementation of the law, domestic stakeholders began to systematically reflect on the development of vaccine supply chain systems, and this process has accelerated further in the post-pandemic era.

Overall, China’s vaccine supply chain system is rapidly improving, but there is still significant variation in the quality of domestic enterprises, leaving a considerable gap compared with international standards. For instance, while China has achieved breakthroughs in certain hardware areas—with companies specializing in chromatography columns and chromatography media emerging as strong players—it still needs to catch up in key core technologies, particularly in chromatography resins. In addition, the quality of domestically produced centrifuges remains inferior to that of imported counterparts.

Given that the domestic supply chain is not yet fully developed, Walvax does not pursue the lowest cost but rather optimal efficiency. For critical materials and equipment, Walvax sources imports. Although imported products entail higher costs, reasonable cost control can be achieved through refined management throughout the entire production lifecycle.

Industry consensus has been reached:The healthy development of the vaccine sector hinges on the seamless integration of all links across the upstream and downstream segments of the industry chain. Domestic enterprises are poised to play a significant role in the vaccine supply chain in the future.

Looking at the present and future, frontier technological innovations in vaccines are presenting historical opportunities for mRNA vaccines, with technological upgrades and global market expansion warranting close attention. China’s vaccine market offers substantial room for growth. According to Frost & Sullivan, the size of China’s vaccine market reached RMB 75.3 billion in 2020, making it the second-largest market globally. The compound annual growth rate (CAGR) of the non-EPI (Expanded Program on Immunization) vaccine market is projected to reach 22.9% during 2020–2025 and 10.9% during 2025–2031. The rapid expansion of the vaccine market will drive increased demand for key upstream raw materials such as culture media. Ensuring a stable supply chain will become critical to vaccine development, and the localization of raw material production and the improvement of supply chains are foreseeable major trends.