When Vaxcyte pushed its 31-valent pneumococcal conjugate vaccine VAX-31 into Phase III clinical trials, a vaccine race surrounding " valence " has entered a heated phase.

01

The debate over technological approaches

The core of market competition in the field of pneumococcal vaccines lies in technological innovation breakthroughs. Traditional multivalent pneumococcal vaccines have consistently faced the dilemma of simultaneously increasing valence and enhancing immunogenicity during their development. Increased valence is often accompanied by a decline in immunogenicity, becoming a key bottleneck for the industry's development. The core regulatory factor in this dilemma is the biological characteristics of the carrier protein.

In the structural system of pneumococcal conjugate vaccines, the carrier protein plays a core role in mediating polysaccharide antigen presentation and activating the body's immune response. However, under traditional technical approaches, high-valent pneumococcal vaccines rely on higher doses of carrier proteins to achieve multi-serotype antigen conjugation. The immunosuppressive effect of the carrier protein itself leads to a decreasing trend in immune response strength as valence increases, resulting in the typical characteristic of "high valence, high efficacy, and weak immunogenicity ." Taking Pfizer's Prevnar series vaccines as an example, Prevnar 13 induced significantly lower immune responses to the seven serotypes shared with the first-generation Prevnar compared to the latter; Prevnar 20 also exhibited a weakened immune response to the 13 serotypes overlapping with Prevnar 13. These results suggest that achieving the dual goals of valence enhancement and immunogenicity maintenance through traditional technical approaches presents significant technical barriers.

Vaxcyte's VAX-24 vaccine, with its cell-free expression system combined with site-specific conjugation technology, offers an innovative solution to overcome the "valence, efficacy, and weakness" dilemma. The core advantage of this technology lies in enhancing carrier protein efficacy through precise regulation of the antigen-carrier binding mode. This reduces the amount of carrier protein used while maintaining or even enhancing vaccine immunogenicity, breaking through the inherent limitations of traditional technologies.

Specifically, VAX-24 employs a modified carrier protein, eCRM , which uses genetic engineering to selectively replace lysine residues with non-natural amino acids (nnAAs). Copper-ion-independent click chemistry is used to optimize antigen-binding sites, enabling precise conjugation of 24 pneumococcal polysaccharide antigens to specific sites on the carrier protein. This targeted conjugation mode effectively avoids spatial shielding of T-cell epitopes, ensuring continuous exposure of key immunotopes. It not only reduces the amount of carrier protein used and avoids its immunosuppressive effects but also achieves highly efficient maintenance of immunogenicity, providing a new technological paradigm for the development of high-cost vaccines.

Clinical trial data show that VAX-24 exhibits differentiated immunogenicity across different populations, with superior performance in the adult population. Topline data from the Phase I/II proof-of-concept trial published in October 2022 indicated that the safety and tolerability of VAX-24 at all dose groups were comparable to those of PCV20; at the standard PCV dose of 2.2 μg, all 24 serotypes met the immunogenicity criteria set by regulatory agencies. Comparative analysis with PCV20 showed that the 20 shared serotypes met the non-inferiority criteria in the opsonization phagocytosis (OPA) test, with 16 serotypes showing significantly stronger immune responses than PCV20; the four VAX-24-specific serotypes all met the superiority criteria. These four serotypes cover 10%-15% of pathogenic strains of community-acquired invasive pneumococcal disease (IPD) in adults, further expanding the scope of protection.

However, VAX-24 did not demonstrate superior immunogenicity in infants. Phase II clinical trial data disclosed in March 2025 showed no statistically significant difference in the level of immune response induced by VAX-24 in infants compared to the Prevnar series vaccines. This result is presumably closely related to the immaturity of the infant immune system; the innate and adaptive immune systems of infants have not yet established a complete response mechanism, and the recognition and activation pathways of vaccine antigens may differ fundamentally from those in adults, thus limiting the effectiveness of this technology in young children.

Despite its limitations in infants, VAX-24's cell-free system and site-specific binding technology remain a milestone. This technology provides a breakthrough approach for the development of high-potency pneumococcal vaccines, effectively overcoming the core bottlenecks of traditional technologies. If immunogenicity issues in younger populations can be addressed through technological optimization, it is expected to lead to a restructuring of global pneumococcal vaccine technology routes, driving the industry towards higher-potency and higher-efficiency vaccines, and providing more comprehensive technical support for the prevention and control of pneumococcal disease.

It is precisely because of the technological advantages validated by the VAX-24 platform that Vaxcyte is confident in escalating the competition and pushing the broader VAX-31 into the final clinical stage. At the heart of this "high-price race" is, in fact, a battle of platform technology .

02

Market structure

Pfizer's Prevnar series of vaccines has long dominated the global pneumonia vaccine market, forming a significant market monopoly advantage. Since its regulatory approval in 2010, Prevnar 13 has rapidly penetrated the global market due to its broad serotype coverage and clear immunoprotective efficacy. Its sales have continued to climb and it has remained among the top vaccines in the global market, with annual sales exceeding US$5 billion.

In recent years, the growth momentum of the Prevnar series vaccines has shown a downward trend, with significant signs of sluggish market growth . According to Pfizer's Q3 2025 financial report, the cumulative sales of its pneumococcal vaccine series (including Prevnar 13) in the first three quarters of 2025 were $4.786 billion, a year-on-year decrease of 1%. This trend is mainly due to two factors: first, the core market is becoming increasingly saturated, narrowing the space for expanding into new markets; second, competing products are being launched one after another, and the market competition landscape is gradually becoming more diversified, squeezing its market share and increasing the growth pressure on Pfizer.

Against the backdrop of Pfizer's slowing market growth, domestic companies are accelerating their expansion in the pneumococcal vaccine field, gradually building differentiated competitive advantages. Watson Bio achieved a breakthrough in domestic production, with its 13-valent pneumococcal polysaccharide conjugate vaccine (Woanxin) approved for marketing at the end of 2019. This successfully broke Prevnar 13's decade-long monopoly in China, marking the official entry of domestically produced pneumococcal vaccines into an era of competition with international giants. In October 2021, Minhai Bio's world's first dual-vector 13-valent pneumococcal vaccine was approved for marketing , becoming a core representative of domestically produced pneumococcal vaccines. This vaccine innovatively uses a dual-vector system of tetanus toxoid (TT) and diphtheria toxoid (DT), which specifically binds to pneumococcal capsular polysaccharides, effectively avoiding the immunosuppressive effect caused by excessive use of a single vector, significantly improving immunogenicity and the durability of the immune response. Since its launch, this product has gained widespread industry recognition for its excellent clinical performance, has been included in the "Patent-Intensive Product Recognition List" for two consecutive years, and has been included in the 2025 edition of the "Chinese Pharmacopoeia," becoming the only 13-valent pneumococcal conjugate vaccine in China to be included in the pharmacopoeia.

Chengda Bio is also actively expanding into the high-priced pneumococcal vaccine market. Its 20-valent pneumococcal conjugate vaccine has entered the preclinical research stage , and it has also obtained an invention patent for "a soluble microneedle patch for a pneumococcal polysaccharide vaccine with an A-shaped structure and its preparation method." This patented technology can precisely control the dosage, improving drug compliance and safety in children, and laying a technological foundation for subsequent clinical translation. From a market positioning perspective, Chengda Bio's pneumococcal vaccines belong to the core vaccine category of the global top 10 best-selling vaccines. Relying on its mature R&D and industrialization platform, it is expected to achieve a breakthrough in the high-priced vaccine sector and possesses broad market prospects.

Besides Watson Bio, Minhai Bio, and Chengda Bio, many other domestic companies are accelerating their R&D efforts in the field of pneumonia vaccines, creating a diversified competitive landscape.
The global pneumonia vaccine market is currently undergoing a restructuring, evolving from a Pfizer-dominated monopoly to a three-way competition characterized by foreign companies maintaining their positions, domestic companies following suit, and technology-driven companies making breakthroughs. Foreign companies like Pfizer, leveraging their first-mover advantage, well-established global sales networks, and mature R&D systems, still hold core market share, but their growth momentum is insufficient. Domestic companies, driven by clinical needs, are gradually establishing a foothold in the domestic market through technological optimization and product iteration, while simultaneously initiating international expansion. Technology-driven companies, represented by Vaxcyte, are leveraging groundbreaking technologies to create differentiated competitiveness in the high-priced vaccine sector, continuously challenging the existing market structure.

03

Future Battlefield

Looking ahead to the global pneumonia vaccine market, driven by increased awareness of disease prevention and control, technological innovation, and unmet clinical needs, the market size is expected to continue to expand. However, it also faces multiple variables that will further reshape the competitive landscape of the industry.

According to authoritative industry forecasts, the global pneumonia vaccine market will reach $13 billion in 2027, with high-priced vaccines (20-valent and above) accounting for a continuously rising proportion and becoming the core driver of market growth. The core logic behind this trend is that high-priced vaccines can cover more highly pathogenic pneumococcal serotypes, significantly improving the breadth and efficacy of immune protection, which meets the clinical need for precise prevention and control.

The US and China exhibit significant differences in their approaches to pneumonia vaccine development, reflecting distinct industrial development strategies and technological orientations. The US, represented by Vaxcyte, adheres to a disruptive R&D philosophy, focusing on groundbreaking innovations in high-potency vaccines . The development of VAX-31 fully demonstrates its aggressive exploration of technological routes. This development path, centered on technological innovation, is expected to overcome existing technological bottlenecks, driving pneumonia vaccines towards higher potency and higher efficacy, and reshaping the global market competition landscape.

China has adopted a steady R&D approach, starting with the domestic production of the 13-valent pneumococcal vaccine to gradually achieve technological accumulation and market breakthroughs. The successful launch of Minhai Biotechnology's dual-vector 13-valent pneumococcal vaccine not only broke the foreign monopoly but also established a mature R&D and industrialization system, laying the foundation for the development of high-valent vaccines. Building on this foundation, companies like Chengdu Biological Products are advancing the development of 20-valent vaccines, forming a development pattern of "gradual upgrading and steady iteration." This approach is well-suited to the domestic industrial technology level and market demand, achieving market penetration through low-cost, low-risk technological iteration and gradually enhancing industry competitiveness.

It must be objectively recognized that the domestic steady approach to vaccine development has significant technological limitations. As vaccine prices increase, the technical challenges related to polysaccharide-antigen conjugation efficiency, immunogenicity regulation, and adverse reaction control increase exponentially, significantly extending R&D costs and timelines. Compared to the disruptive approach adopted by the United States, domestic companies still lag behind in innovation and breakthrough capabilities in high-end technologies, urgently requiring increased investment in basic research, strengthened efforts in tackling core technologies, and breakthroughs in the technological bottlenecks of high-priced vaccine development.

It is worth mentioning that the restructuring of the global pneumonia vaccine market is subject to the comprehensive regulation of three core variables: clinical trial results, regulatory approval pace, and medical insurance payment policies , which directly determine the market competitiveness and development fate of enterprises.

04

Conclusion

The competition in pneumonia vaccine development has moved beyond simply having a vaccine; it has entered a new phase where quantity and quality are equally important. Pfizer's growth trajectory suggests that even giants have their limits; while Vaxcyte's technological ventures and the steady strategic moves of Chinese companies together outline the industry's future possibilities. In this multi-billion dollar game, only companies that truly overcome technological barriers and precisely address clinical needs will be able to weather the cycles and win in the future.

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