--- title: "The Birth of China's Nine-Valent HPV Vaccine" type: "Topics" locale: "zh-CN" url: "https://longbridge.com/zh-CN/topics/31955706.md" description: "At 499 yuan per dose, Wantai Biotech has provided the general public with a second option beyond imported 9-valent HPV vaccines through its socially responsible pricing. As the first domestically produced and the second globally approved 9-valent HPV vaccine, Wantai Biotech's Cecolin®9 has garnered widespread market attention since its approval. As early as July 2023, The Lancet Infectious Diseases published head-to-head clinical trial data, showing that the domestically produced 9-valent HPV vaccine has comparable immunogenicity and safety to the imported 9-valent HPV vaccine..." datetime: "2025-07-18T04:12:59.000Z" locales: - [en](https://longbridge.com/en/topics/31955706.md) - [zh-CN](https://longbridge.com/zh-CN/topics/31955706.md) - [zh-HK](https://longbridge.com/zh-HK/topics/31955706.md) author: "[锦缎研究院](https://longbridge.com/zh-CN/profiles/2576456.md)" --- > 支持的语言: [English](https://longbridge.com/en/topics/31955706.md) | [繁體中文](https://longbridge.com/zh-HK/topics/31955706.md) # The Birth of China's Nine-Valent HPV Vaccine At 499 yuan per dose, Wantai Biotech has provided the general public with a second choice beyond imported 9-valent HPV vaccines through its socially responsible pricing. As China's first and the world's second 9-valent HPV vaccine, Cecolin®9 by Wantai Biotech has garnered widespread market attention since its approval. As early as July 2023, The Lancet Infectious Diseases published head-to-head clinical trial data showing that the domestic 9-valent HPV vaccine demonstrated comparable immunogenicity and safety to the imported 9-valent HPV vaccine, leading to speculation that Cecolin®9 would also benchmark its pricing against imported products. However, Wantai Biotech's final decision exceeded all expectations, with Cecolin®9 priced at only 40% of the imported 9-valent HPV vaccine. Given equivalent efficacy, such pricing will undoubtedly help Cecolin®9 rapidly capture domestic market share. Wantai Biotech's "conscience" pricing is not a price war tactic for market capture but rather the result of an "18-year refinement" achieving next-generation transformation. Vaccine pricing balances political, social, R&D, and cost factors. On the social benefit side, this pricing will significantly contribute to WHO's "Accelerated Plan to Eliminate Cervical Cancer (2023-2030)", while on the other side, many may not fully appreciate the arduous journey of domestic 9-valent HPV vaccine development. ## **01 Disruption Starts from the Foundation** True disruption often begins with changes at the foundational level. Wantai Biotech's breakthrough in 9-valent HPV vaccine originated from the most fundamental protein expression system. Vaccines are biological products prepared from artificially processed pathogenic microorganisms or their components to prevent corresponding infectious diseases. Traditional vaccines often use attenuated pathogens, while genetic engineering vaccines clone gene fragments encoding protective antigens into expression vectors to produce virus-like particles (VLPs) structurally similar to natural viruses. Since HPV cannot be cultured in vitro, making traditional vaccine preparation impossible, genetic engineering became the mainstream R&D direction for HPV vaccines. After years of effort, Chinese scientist Zhou Jian and Australian immunologist Ian Frazer successfully expressed HPV VLPs in 1991, verifying their ability to induce immune responses—this became the core technology for subsequent HPV vaccine development. Figure: VLP-based vaccine production process. Source: Zhongtai Securities Guided by VLP theory, Merck developed the quadrivalent HPV vaccine, and GSK the bivalent HPV vaccine. Throughout HPV vaccine production, the choice of protein expression system is the most fundamental yet critical step. Leveraging first-mover advantage, GSK and Merck established extensive patent networks in China, with core patents covering "eukaryotic cell expression technology"—GSK using baculovirus-insect cell systems and Merck yeast systems. Since natural viruses express proteins in human cells, eukaryotic systems resembling human cells were preferred, making "eukaryotic cell expression technology" a bottleneck controlled by foreign companies. When Xia Ning Shao's team at Xiamen University began HPV vaccine R&D, the biggest challenge was this patent barrier. As Kazuo Inamori said, "The most effective way to overcome difficulties is persistence!" Facing this barrier, Xia's team chose innovation at the source. When the eukaryotic path was blocked, they pursued "prokaryotic cell expression systems," then considered "almost impossible" by international academia. The main drawback of prokaryotic systems is their lack of advanced protein processing. Expressing a single protein is easy, but forming multiprotein complexes with activity is challenging. The conventional approach—expressing proteins first then restoring activity—had no prior success. Figure: Comparison of protein expression systems. Source: Guosheng Securities Clearly, Xia's team was pioneering an unprecedented difficult path, but they weren't alone. Behind them stood a strong supporter—Zhong Shanshan. As early as 1997, Xia's team collaborated with Wantai Biotech on diagnostic reagents. By 2000, they established a joint lab, laying the foundation for vaccine R&D. At that time, Zhong's Yangshengtang was thriving, but he focused on life sciences, acquiring Wantai Biotech as an R&D platform. Xia's team was one of four academic teams Zhong partnered with, and today, only Xia's team "survived" with continuous output. With Zhong's support, Xia's team first validated the E. coli VLP platform via hepatitis E vaccine R&D. In 2002, the "E. coli expression system" successfully produced active hepatitis E pORF2 protein and abundant monoclonal antibodies, proving its potential for human vaccine production. This "almost impossible" path was finally validated through tens of thousands of experiments by Xiamen University's team. ## **02 A Million Iterations** After overcoming the expression system hurdle, Xia's team faced not smooth sailing but arduous years. The year after validating the E. coli system, they launched the bivalent HPV vaccine project—a journey spanning over two decades. The biggest challenge was making E. coli "obediently" simulate viral protein production, involving gene modification and protein purification/refolding. Post-expression antigens must assemble into VLPs resembling natural viruses to function as vaccines. This requires precise pairing of cysteine residues, correct disulfide bonds, and properly conformed pentamers. Without precedents, Xia's team worked blindly, persevering without shortcuts. After accumulating experience, Wantai Biotech officially started 9-valent HPV vaccine R&D in 2007. Zhang Jun, Dean of Xiamen University's School of Public Health, admitted: "9-valent HPV vaccine R&D was far harder than expected. It's not simply stacking independent vaccines but integrating nine antigens into 0.5mL without interference. Each added type increases difficulty exponentially." To improve efficiency, Wantai adopted an "amoeba" organizational structure—small teams each handling one HPV type, later expanding to 2-3 types. Initially, Wantai's R&D team collaborated with Xiamen University postgrads: Wantai focused on downstream process development; the university handled cloning, animal tests, and upstream research. Throughout 9-valent R&D, the team constantly battled challenges. For instance, assembling one type's proteins into particles took three years, with some postgrads delaying graduation by six months. One student, after repeated failures, nearly lost confidence, saying "this is impossible—anyone attempting it will fail." But persistence paid off. Countless failures accumulated experience until, after a million experiments, the team found the solution. In 2017, they obtained clinical approval; 2018 monkey efficacy tests confirmed validity; 2019 saw clinical trials launch. After over 20 years, Wantai Biotech finally reaped rewards. In 2019, its bivalent HPV vaccine (Cecolin®) became China's first domestically developed HPV vaccine; in 2025, its 9-valent HPV vaccine (Cecolin®9) became the world's second approved 9-valent HPV vaccine. To compare immunogenicity and safety, Wantai conducted a head-to-head study between Cecolin®9 and Gardasil®9 in 2021. Enrolling 488 healthy women (18-26 years), results showed 1 month post-full vaccination, both groups had 100% seroconversion for all nine types. Cecolin®9's neutralizing antibody geometric mean concentrations (GMCs) for HPV 6/31/45/52/58 were slightly higher, with comparable GMCs overall. Adverse reaction rates were 42.6% (Cecolin®9) vs. 47.3% (Gardasil®9), demonstrating good safety. Figure: Cecolin®9 vs. Gardasil®9 neutralizing antibodies. Source: The Lancet Infectious Diseases Functional neutralizing antibodies are scientifically recognized as HPV vaccines' main protective mechanism. This rigorous study proved Cecolin®9 induces Gardasil®9-comparable antibodies, indicating similar efficacy. Additionally, Wantai plans higher-valency HPV vaccines (e.g., 21-valent) covering \>99% of HPV types, reducing screening reliance. Mastering basic techniques can create killer apps. Cecolin®9's breakthrough stemmed from 18 years and a million iterations—"quantity" triggering "quality." ## **03 Systemic Evolution** Cecolin®9 represents not just R&D innovation but full production process evolution. Post-approval, how to produce at scale? Li Zhongyi, Wantai's Production Director, explained: "Xiamen University handles concept validation—proving products prevent disease. After validation, R&D develops processes for small/medium trials, clinical tests, plus commercial facility design/build. Production control ensures sterile, enclosed transfers minimizing contamination risks." Li outlined three complex stages: 1) Bulk production (fermentation & purification)—engineered E. coli expresses antigens, extracted via homogenization/centrifugation; 2) Formulation (mixing & sterile filling); 3) Inspection & packaging. Traditional quality control relied on testing. Later, people realized testing's limits—quality depends more on processes. Now, the paradigm shifted further: good quality is designed in. Cecolin®9 embodies this—R&D deeply considers process design/selection, choosing industrially scalable techniques/equipment, building smart production lines meeting international standards. A core team member recalled E. coli-expressed HPV VLP R&D hardships. During process development, one type's production issue nearly broke a postgrad, who tearfully persisted until solving it. Misfortune may be blessing in disguise. Though prokaryotic systems posed R&D challenges, once overcome, their efficiency shines—E. coli cultures take ~20 hours vs. weeks for yeast/cells, enabling mass production and cost savings. Building on bivalent HPV experience, Wantai optimized 9-valent production. Through thousands of experiments and unconventional approaches, they created robust processes maximizing batch yields/efficiency, enabling 20M annual capacity. Academic, R&D, and process evolution collectively enabled Cecolin®9's epic advancement. ## **04 Vaccines Should Be Inclusive** No success comes easy—someone must bear the weight. Eighteen years and a million iterations underpin Cecolin®9's socially responsible pricing and imported-vaccine-matching quality. Wantai is conducting male clinical trials for 9-valent HPV vaccine to prevent genital warts, penile/perineal/anal cancers, etc. Five years ago pre-Cecolin®, China relied on imports—GSK's bivalent at 580 yuan/dose; Merck's 9-valent at 1,298 yuan/dose, both requiring three doses. Despite high prices, supply shortages made even "appointment fees" hundreds extra. Imported HPV vaccines were neither affordable nor accessible. Wantai's breakthrough eased shortages, even making bivalent HPV vaccines public health programs regionally. Monopolies maximize profits; competition restores rationality. Imported vaccines solve problems but can't meet China's massive needs at high prices. Beyond domestic gaps, Wantai accelerates globalization—Cecolin® approved in Morocco, Nepal, Thailand, DR Congo, Cambodia, spreading inclusivity worldwide and elevating China's vaccine influence. WHO's 2020 "Global Strategy to Accelerate Cervical Cancer Elimination" requires China's vaccines for success. Though technologically advanced, vaccines aren't luxuries. Only mass adoption spreads R&D costs, defining their inclusive nature. Thus, vaccines shouldn't serve few at high prices but many at fair ones. This logic dictates cost-conscious Chinese vaccines can restore inclusivity. They'll become global vaccine "game-changers." This article is based on public information for communication only, not investment advice. ### 相关股票 - [Wantai Biological (603392.CN)](https://longbridge.com/zh-CN/quote/603392.CN.md)