Frost & Sullivan releases 'Human Vaccines Market research report': A vast expanse of blue waters, with a multitude of vessels vying for dominance (full text available here)

Total word count: 6,403, Reading time for comprehension: 10 minutes

Vaccines are biological products made from pathogenic microorganisms or their components and metabolites, using biotechnology for preparation. They are used to prevent and treat corresponding human diseases. After vaccination into the human body, they can stimulate the immune system to produce specific humoral and/or cellular immune responses, enabling the body to acquire immunity against the corresponding pathogenic microorganisms.

Source: Literature search, Frost & Sullivan analysis

From a clinical perspective, vaccines are divided into preventive and therapeutic vaccines; in terms of technical approaches, vaccines are mainly categorized into attenuated live vaccines, inactivated vaccines, toxoid vaccines, polysaccharide (conjugate) vaccines, recombinant protein vaccines, nucleic acid vaccines, and viral vector vaccines.

The Report details the definition, development history, mechanism of action, technical pathway comparison, analysis of vaccine R&D trends, and the impact of the COVID-19 pandemic on the human vaccine industry. For more detailed content, please refer to the full report.

Adjuvants refer to substances that can assist in antigen responses, regulate the intensity and type of immune responses. The functions of adjuvants include enhancing the immunogenicity of antigens in products, altering the nature of immune responses, reducing the amount of antigen and number of immunizations required for successful immunity, and improving the immune response in populations with immune deficiencies.

Source: Literature search, Frost & Sullivan analysis

According to the FDA's 'Regulatory Considerations for the Safety Evaluation of Adjuvants and Adjuvant-Prepared Vaccines', adjuvants can be broadly divided into three categories. The first category includes adjuvants that enhance antigen presentation by antigen-presenting cells and/or lymph nodes, thereby improving immune responses. Examples include aluminum salts, oil-in-water emulsions (such as Novartis' MF59 and GSK's AS03), and liposomes. The second category includes immunostimulants, also known as immune enhancers. They primarily regulate the quality of immune responses through signal transduction mediated by receptors. For instance, PIKA double-stranded RNA and MPL can activate Toll-like receptors 3, 4, QS21, CpG, cytokines, and more. Finally, the third category is composed of combinations of the first two types, known as combination adjuvants or 'adjuvant systems'.

The Report details the classification, development challenges, and future trends of vaccine adjuvants. For more detailed content, please refer to the full report.

The Report analyzes the market scale of human vaccines in China and globally, sales of leading vaccine manufacturers, approved and under-development vaccine products, market drivers, and future development trends. For more detailed content, please refer to the full report.

Human papillomavirus (HPV) is the most common viral infection of the reproductive tract and can be transmitted through skin contact during sexual activity. Based on the different risks associated with various types of HPV and cervical cancer, they are classified into high-risk and low-risk types. Different types of human papillomavirus (HPV) can lead to different types of infections; low-risk HPV infections can cause visible genital condyloma acuminata as well as asymptomatic cervical, vaginal, vulvar, urethral, penile, anal condyloma acuminata, and common skin warts; high-risk HPV infections can lead to cancer. Worldwide, the carcinogenic rate of high-risk HPV strains is about 5%, with cancers caused including cervical cancer, anal cancer, head and neck cancer, penile cancer, vaginal cancer and vulvar cancer, oropharyngeal cancer.

Source: SGS, Frost & Sullivan analysis

As of December 31, 2022, there are five HPV vaccines approved for marketing in China, all using recombinant protein vaccine technology; there are a total of 20 human papillomavirus vaccines in clinical research stages in China, with fierce market competition.

According to statistics, in 2021, China's HPV vaccine batch release volume was 29.602 million doses. GARDASIL and GARDASIL 9 from Merck & Co. accounted for the majority of the market share. Domestic bivalent vaccines currently hold a lower market share due to their late approval time.

Source: SGS, Frost & Sullivan analysis

The Report details the approved HPV vaccine products in China and the pipeline under development, and analyzes the driving forces for the development of the HPV vaccine market and its future trends. For more detailed content, please refer to the full report.

The varicella-zoster virus is one of the eight herpesviruses known to cause human infection and is distributed worldwide. VZV infections clinically cause two different disease forms: varicella and zoster. The disease is mainly transmitted through inhalation of virus-containing droplets, direct contact with varicella or zoster rash, or aerosols. With increasing age, the proliferation ability of VZV-specific T cells declines, weakening cellular immunity, making it easier for VZV latent in nerves to be activated. In recent years, studies have shown that the incidence of zoster tends to be younger, especially among people with sub-health status, tumors, AIDS patients, and other immunocompromised individuals.

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Herpes zoster usually affects the skin of the chest and waist, but can also involve the geniculate ganglia, ophthalmic trigeminal ganglia, and oral cavity. In severe cases, it may lead to postherpetic neuralgia (PHN), imposing a significant disease burden on patients.

Source: Literature search, Frost & Sullivan analysis

The main herpes zoster vaccines used globally are divided into two types: live attenuated herpes zoster vaccines and recombinant herpes zoster vaccines. The live attenuated herpes zoster vaccine was initially developed and marketed by Merck but has not yet been launched in China. The only approved herpes zoster vaccine in China is GSK's Shingrix, which is prepared using recombinant protein technology. As of December 31, 2022, there are a total of 7 herpes zoster vaccines in clinical development phase in China, including 4 live attenuated vaccines and 3 recombinant protein vaccines.

According to statistics, in 2020 and 2021, the batch release volume of varicella-zoster vaccines in China was 1.6 million and 0.6 million doses respectively, with output value scales of 26 billion and 900 million RMB respectively.

Source: FDA, NMPA, EMA, literature search, Frost & Sullivan analysis

The Report details the approved zoster vaccines in China and the pipeline under development, and analyzes the driving forces and future trends of the zoster vaccine market development. For more detailed content, please refer to the complete report.

The rabies virus is a ribonucleic acid-based bullet-shaped virus that is highly contagious in mammals such as dogs and cats. Once clinical symptoms appear after infection, the fatality rate is almost 100%, making it one of the most lethal infectious diseases in the world.

The global annual number of rabies deaths is about 59,000 cases, mainly occurring in Asia and Africa. China is an epidemic country for rabies. According to data from the Chinese Center for Disease Control and Prevention, there are about 40 million people exposed to rabies in China each year, while the vaccination rate among these exposed individuals is only about 35%. In 2021, the reported number of rabies deaths ranked fifth among legally reportable infectious diseases, posing a serious threat to the lives and health of the people.

Currently, there are no effective clinical methods for treating rabies, so post-exposure prevention is crucial. This is mainly achieved through vaccination with human rabies vaccine and injection of passive immunization preparations.

Source: Literature search, Frost & Sullivan analysis

The human rabies vaccine market can be divided based on the different cell matrices used for vaccine culture. Different cell matrices have distinct characteristics and require different manufacturing processes. Currently, the cell matrices used for rabies vaccine production include primary cells (murine kidney cells and chicken embryo cells) and subcultured cells (Vero cells and human diploid cells).

As of December 31, 2022, there are a total of 20 human rabies vaccines approved for marketing in China, including 13 human rabies vaccines (Vero cells), 6 human rabies vaccines (murine kidney cells), and 1 human rabies vaccine (human diploid cell); there are also 24 human rabies vaccines in clinical research phase in China, including 13 Vero cells, 8 human diploid cells, and 3 chick embryo cells.

From 2017 to 2021, the batch issuance volume of rabies vaccines in China showed a fluctuating trend, first declining and then rising. Affected by the Changchun Changsheng vaccine incident in 2018, as well as issues with GMP certification for Ningbo Rong'an and Guangzhou Nuocheng, the batch issuance volume of rabies vaccines in China continued to decline from 2018 to 2019. The COVID-19 pandemic has led to reduced outdoor activities and travel time for residents, extended contact time with animals at home, increased risk of rabies exposure, and thus an increase in demand for rabies vaccines. In 2021, the batch issuance volume of rabies vaccines in China was 880,000 doses, a 12.0% increase compared to 2020.

Source: SGS, Frost & Sullivan analysis

From 2017 to 2021, the output value of the human rabies vaccine market in China showed a fluctuating trend, first declining and then rising. Affected by the suspension of production by some rabies vaccine manufacturers, the decline in the batch issuance volume of rabies vaccines from 2018 to 2019 led to a reduction in output value scale. In 2020, with stricter supervision of the vaccine industry and improvements in rabies vaccine production technology, the production cost of rabies vaccines increased, resulting in an increase in the winning bid prices of rabies vaccines by various enterprises in provinces such as Shanghai, Hebei, Inner Mongolia, and Hainan. At the same time, with the increase in vaccination rates and the entry of high-value rabies vaccines into the market, the output value scale increased. As of 2021, the output value scale of human rabies vaccines in China reached approximately 9.4 billion yuan.

Source: SGS, Frost & Sullivan analysis

In terms of cell type breakdown, 88.8% of rabies vaccines in China are produced using Vero cell technology based on batch release volume. This is related to the large number of manufacturers approved for Vero cell rabies vaccines, their high production volume, and low prices, which offer a certain cost-performance ratio. Human diploid cell vaccines and murine kidney cell vaccines account for 5.8% and 5.4% respectively.

Source: SGS, Frost & Sullivan analysis

In the United States, 71.3% of rabies vaccines are produced using chicken embryo cells, with human diploid cell vaccines accounting for 28.7%. This may be related to the high cost per dose and low production volume of human diploid cell vaccines.

Source: MIDAS, Frost & Sullivan analysis

The Report details the approved human rabies vaccine products in China and the ongoing research pipelines, and analyzes the driving forces for the development of the human rabies vaccine market as well as its future trends. For more detailed content, please refer to the full report.

Source: Literature search, Frost & Sullivan analysis

Influenza viruses are classified into types A, B, C, and D based on the antigenicity of their nucleoprotein and matrix proteins.

Source: Literature search, Frost & Sullivan analysis

People of all ages can be infected with influenza, mainly occurring in high-risk groups such as the elderly, young children, obese individuals, pregnant women, and those with chronic underlying diseases (such as asthma, diabetes, or heart disease), who are more likely to develop severe influenza or even die. Annual influenza vaccination is an effective means of preventing influenza, which can significantly reduce the risk of infection and serious complications in vaccinated individuals.

As of December 31, 2022, there were a total of 22 influenza vaccines approved for marketing in China, including 7 quadrivalent influenza vaccines and 15 trivalent influenza vaccines. Most of the influenza virus vaccines under clinical research are quadrivalent, with a total of 17 vaccines in clinical research phase as of the statistical time.

Looking at the trend of approval and issuance volume from 2017 to 2021, there was a significant decline in approval and issuance volume in 2018, followed by a gradual recovery over the next three years. In 2018, due to various reasons such as the Changchun Changsheng vaccine incident and power outages at Beijing Sinovac's factory, many vaccine companies stopped supplying influenza vaccines. In 2019, approval and issuance returned to normal, but due to the low vaccination rate in previous years and the long production cycle of influenza vaccines, manufacturers were unable to prepare in advance, resulting in a 'hard-to-find' situation during the influenza outbreak in 2019. In 2020, affected by the COVID-19 pandemic, the National Health Commission vigorously promoted and implemented measures, gradually increasing public awareness of preventing influenza and significantly enhancing vaccination intentions. Coupled with increased production capacity by manufacturers, the approval and issuance volume of influenza vaccines reached a new high in 2020. The quadrivalent inactivated influenza vaccine has seen rapid growth since its launch in 2018, with the approval and issuance volume of quadrivalent influenza vaccines exceeding that of trivalent influenza vaccines in 2020, becoming the most prevalent variety.

Source: SGS, Frost & Sullivan analysis

In 2021, the output value scale of China's influenza vaccine market was approximately 6.1 billion yuan, mainly driven by overall factors such as increased health awareness and government support for national immunization. In addition, considering that developed countries generally use quadrivalent influenza vaccines, China's influenza vaccine market will also be replaced by quadrivalent vaccines, and it is expected to experience rapid growth in the future.

Source: Literature search, Frost & Sullivan analysis

The Report details the approved influenza vaccine products and ongoing research pipelines in China, and analyzes the driving forces and future development trends of the influenza market. For more detailed content, please refer to the full version of the report.

Pneumococcus is a common Gram-positive bacterium found in the nose and throat, often colonizing the respiratory tract and oral cavity. Normally, pneumococcus does not cause disease, but when its host environment changes, it can lead to infection. Bacterial pneumonia caused by pneumococcus is one of the important causes of morbidity, hospitalization, and even death in children and the elderly worldwide, accounting for 80% of human infectious pneumonias.

Source: China Health Statistics Yearbook, analysis by Frost & Sullivan

Due to the serious problem of antibiotic resistance in the treatment of pneumococcal diseases, pneumococcal vaccination is currently the most effective way to combat these diseases. Pneumococcal vaccines mainly include two types: 13-valent pneumococcal polysaccharide conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine.

As of December 31, 2022, a total of 3 13-valent pneumococcal polysaccharide conjugate vaccines and 5 23-valent pneumococcal polysaccharide vaccines have been approved for marketing in China; 9 13-valent pneumococcal polysaccharide conjugate vaccines and 4 23-valent pneumococcal polysaccharide vaccines are in clinical research phase.

As of the end of 2021, the total batch issuance of PCV13 was approximately 17.56 million doses, a year-on-year increase of 61.2%. Since the 23-valent pneumococcal vaccine can only induce humoral immunity by producing antibodies rather than adaptive immunity, and is ineffective against children under 2 years old, the growth rate of the 23-valent pneumococcal vaccine batch issuance has been slow. In 2021, affected by the COVID-19 vaccination campaign, the total batch issuance of PPSV23 decreased to approximately 10.61 million doses.

Source: SGS, Frost & Sullivan analysis

PCV13 and PPSV23, due to their excellent protective efficacy, can significantly reduce mortality rates in children and the elderly respectively, offering good cost-effectiveness. Therefore, they have become blockbuster non-immunization program vaccines. From 2017 to 2021, the output value scale of China's pneumococcal vaccine market increased by a compound annual growth rate of 74.0%, with PCV13 accounting for the main market.

Source: SGS, Frost & Sullivan analysis

The Report details the approved pneumococcal vaccine products in China and the pipeline under development, and analyzes the driving forces for the development of the pneumococcal market as well as its future trends. For more detailed content, please refer to the full report.

The Report details the financing situation of Chinese vaccine R&D companies, vaccine enterprise cooperation and development, vaccine pipeline transactions, and mergers and acquisitions of vaccine enterprises. For more detailed content, please refer to the full report.

Liaoning Chengda Biotechnology Co., Ltd. (stock code: 688739) was founded in June 2002 and is a biotechnology company focusing on the research, development, production, and sales of human vaccines. Chengda Biotechnology has been deeply involved in the field of human vaccines for many years. Through independent research and innovation, it has built the "process platform technology for large-scale preparation of vaccines using bioreactors," breaking through the technical challenge of producing high-quality vaccines through large-scale cell culture during the vaccine production process.

The company has currently formed an industrialization echelon, with one rabies vaccine, 'Chengda Suida', available.^®"and one Japanese encephalitis vaccine" "Chenglibao^®"Going public, the company currently has six vaccines in clinical trial stages, covering a variety of diseases including rabies, influenza, meningococcal meningitis, pneumococcal infection, and hepatitis A.

Shanghai Qingsai Biotechnology Co., Ltd. was established in Jinshan District, Shanghai in April 2017 and was nominated for the "2022 China's New Pharmaceutical Innovators" list in December 2022. Qingsai Biotechnology focuses on the research and development and industrialization of human vaccines. It possesses a virus reverse genetic technology platform that enables precise targeted modification of the viral genome at the genetic level to efficiently obtain recombinant virus strains with specific phenotypes. It also has a vaccine product evaluation and testing technology platform that can construct and evaluate vaccine production strains, establish corresponding testing methods, and lay a foundation for the development of innovative vaccines.

Qingsai Biotech's R&D pipeline consists of 6 varieties, covering three infectious diseases including rabies, mumps, and rotavirus infection. Among them, the company's developed human rabies vaccine is the first clinical-stage rabies vaccine in China using chicken embryo fibroblast cells as the production cell matrix; the company's genetically recombinant live attenuated mumps vaccine developed through a viral reverse genetic manipulation technology platform is the world's first non-A genotype live attenuated mumps vaccine to enter clinical research.

Jiangsu Ruike Biotechnology Co., Ltd. (Stock Code: 02179.HK) was founded in 2012. It is an innovative vaccine company driven by independent R&D technology, dedicated to creating innovative vaccines covering R&D, production, and commercialization. The company has been deeply involved in the vaccine field for many years and has currently established four innovative technology platforms: advanced new adjuvants, protein engineering, immunological evaluation, and mRNA vaccines.

The company is one of the few in the world capable of developing novel adjuvant systems, and it takes the novel adjuvant platform as its core, collaborating with antigen optimization design and immunological evaluation technologies to continuously develop heavyweight vaccine varieties with leading performance. The company has a rich pipeline of research projects, including a total of 12 clinical research programs, covering multiple diseases including cervical cancer and genital warts, COVID-19, herpes zoster, adult tuberculosis, influenza, and hand, foot and mouth disease.

Yisheng Biopharmaceutical Co., Ltd. is a global professional biopharmaceutical company integrating R&D, production, and sales, dedicated to developing innovative biological therapeutic drugs against tumors and viral infections. The company owns a globally unique PIKA Picaric Immunomodulation Technology Platform with independent intellectual property rights, and has developed innovative vaccines and therapeutic biologics. The company's Picaric technology and vaccine products have received support three times for the 'National New Drug Creation Project'.

Ebiosciences has launched the market-ready Ebsen Jun'an rabies vaccine, with a research and development pipeline including the Pika rabies vaccine, Pika recombinant protein COVID-19 vaccine, Pika immunotherapy for cancer, Pika hepatitis B vaccine, Pika influenza vaccine, and other products. Biosciences has wholly-owned R&D centers in Beijing, Singapore, and Maryland, USA, and a large-scale GMP vaccine production base in Shenyang, China. The PIKA immunomodulatory technology developed exclusively by Biosciences has received a total of 60 patents in more than 30 countries around the world.