In October 1979, more than 180 years after the founding of modern vaccine science, Edward Jenner, the father of immunology, founded in Nairobi, Kenya, in October 1979, the World Health Organization announced that "the world has eliminated smallpox." In the 20th century alone, thi

Modern Founder of microbiology and inventor of rabies vaccine Louis Pasteur.

Talking about the role of vaccines in more than two centuries, Triomphe said that infectious diseases had high incidence and mortality rates in pre-vaccine eras. A serious infectious disease may even change the direction of a nation, a country, and even the entire human history. In the vaccine era, such threats have been greatly reduced.

In addition to smallpox, he took another infectious disease that is expected to be eliminated, polio (i.e. polio ), as an example. In the past 30 years, polio vaccine has saved more than 18 million people from paralysis or death. "We are working with the international community to work hard to eliminate polio. Over the past 20 years, more than 1.1 billion children worldwide have been immunized, saving up to 3 million lives each year and helping to reduce the mortality rate of children in half."

According to WHO data, polio is currently only prevalent in two countries: Afghanistan and Pakistan . The boundaries of preventable diseases continue to expand in the 21st century, and for vaccine giants like Sanofi, "there is still a lot of room for improvement." Triomphe pointed out that before the outbreak of the new crown epidemic, a vaccine revolution had quietly begun, and the new crown epidemic accelerated this process.

This vaccine revolution includes new technologies such as mRNA that are adding new tools to our preventive medicine toolbox. Speaking of mRNA, a "dark horse" in the COVID-19 pandemic, Triomphe said that the mRNA vaccine can directly produce "mimics" of viruses or bacteria. These "mimics" will be recognized and activated by the immune system, so that the human body can resist real disease infection in the future. "The DNA in human cells is like a masterpiece of a masterpiece. Its composition is excellent, but the conductor needs to convert it into beautiful music, and mRNA happens to be such a conductor."

In the field of new crown vaccine , Sanofi and GlaxoSmithKline have sought regulatory approval in Europe for the first generation of new crown vaccine jointly developed by both sides. Relevant research data show that as a general enhancement injection, it can improve the level of neutralizing antibodies against all currently approved COVID-19 vaccine platforms. The two companies will submit final applications to the U.S. FDA and other global regulators in the coming weeks.

Triomphe is also happy to see mRNA technology being applied to the new crown vaccine. He said, "This technology that had appeared before the COVID-19 pandemic has now become a very timely and popular solution. Against the backdrop of the COVID-19 pandemic, widespread attention and large-scale investment in mRNA technology have accelerated its success."

Triomphe also mentioned that mRNA technology is still in its infancy and needs further improvement to be applied to conventional vaccine vaccination, "especially, it needs to be improved in terms of thermal stability and tolerance."

It is worth noting that in August 2021, Sanofi acquired Translate Bio, a clinical-stage mRNA treatment company, for a total of about US$3.2 billion. The cooperation between the two was earlier. In June 2018, Sanofi and Translate Bio reached a R&D cooperation agreement to develop mRNA vaccines; this agreement was further expanded in 2020 to solve a variety of diseases that may occur now and in the future.

At the end of June 2021, Sanofi also created a new center of excellence for mRNA vaccines and announced that it would invest approximately 400 million euros per year. "This will not only accelerate the research and development of our mRNA vaccine portfolio, but will also bring more help to new vaccines developed with mature technologies." Triomphe believes that although mRNA technology cannot be a solution to all diseases, converting it into conventional disease prevention methods may have a huge impact on many unmet public health needs.

"Now, it has become a key new technology in our "integrated vaccine development arsenal" and is expected to reshape the pattern of health protection in the future." For Sanofi, mRNA technology will develop in coordination with other existing platforms including inactivated vaccine , polysaccharide vaccine, recombinant vaccine, subunit vaccine, viral vector vaccine, etc.

Triomphe revealed that in terms of vaccine research and development, it is expected that by 2025, Sanofi will conduct human clinical trials on 10 candidate vaccines, 6 of which will use mRNA technology.

mRNA vaccine principle

Seeking the first or best new vaccine of the same type

mRNA technology platform innovation is one of the important development directions of new vaccine technologies. From vaccine research and development, production to vaccination, Triomphe believes that new technologies run through the whole process, "Technology is an effective way to achieve goals." Which areas are targeted at

to layout is itself a "innovation science." "We will give priority to those who can successfully bring new vaccines to people around the world that are the first or the best in the same category."

For Sanofi's vaccine business, influenza is an important area of ​​layout. According to the 2021 Sanofi financial report, the sales of the vaccine division last year were 6.323 billion euros, an increase of 6.8% compared with the same period in 2020, among which the sales of influenza vaccines reached a record level. "Every year, we provide more than 250 million doses of influenza vaccines worldwide, and influenza is an important area where we are accelerating the development of the next-generation vaccine."

It is reported that Sanofi will launch clinical research on the quadrivalent influenza mRNA candidate vaccine in 2022. "In the field of influenza mRNA vaccines, we always remember that the tolerance and thermal stability of new influenza vaccines must be equal to or better than existing vaccines." Triomphe said that in the development of next-generation influenza vaccines, Sanofi's goal is to provide products with higher protective efficacy than existing vaccines, which means that there is a need to provide protection for diseases other than influenza and reduce the risk of other serious diseases after influenza, such as hospitalization for myocardial infarction, pneumonia or stroke .

In fact, this demand is particularly urgent among the elderly over 60 years old. Overall, the elderly are the key group for flu prevention. This group has a weak immune system and is often accompanied by chronic diseases in addition to being susceptible to infection. Previous studies have shown that even in healthy adults, the likelihood of a myocardial infarction after influenza is 10 times more likely than when it is not infected.

"Influenza vaccination is the best public health measure to prevent influenza and its complications, but studies show that due to the weak immune system of the elderly, traditional influenza vaccines are not as effective as those of other age groups. To this end, Sanofi has been developing and launching a new influenza vaccine for the past decade." Triomphe introduced, "For example, we used a brand new recombinant technology to prepare a differentiated vaccine that can better match the antigen with the epidemic strain." It is reported that compared with the standard dose of tetravalent influenza vaccine, the antigen content of the recombinant tetravalent influenza vaccine is three times that of it. In people aged 50 and above, the relative effectiveness of preventing influenza diagnosed by PCR has been increased by 30%. The vaccine was approved in Hong Kong, China in April last year.

In China, among the excess respiratory deaths caused by influenza, 80% of the elderly over 60 years old account for. Triomphe said, "At present, more and more enhanced influenza vaccines are being widely used worldwide, and they can better protect the elderly from influenza."

In addition to influenza, Sanofi is also planning to unmet new areas such as respiratory syncytial virus , acne , chlamydia infection , etc.Triomphe takes respiratory syncytial virus as an example. For more than 60 years, many vaccine manufacturers have been developing prevention methods for respiratory syncytial virus, but few breakthroughs have been made.

Respiratory syncytial virus is the most common viral pathogen that causes acute lower respiratory tract infection (LRTI) in infants and young children worldwide. It is also the leading cause of hospitalization for all infants, with most respiratory syncytial virus-related hospitalizations occurring in healthy babies born in full term. In 2015, there were about 33 million new cases of lower respiratory tract infections with respiratory syncytial virus worldwide, resulting in more than 3.2 million patients being hospitalized and about 60,000 children under 5 years of age died in the hospital.

The New England Journal of Medicine (NEJM) published positive results for a Phase 3 trial that evaluated nirsevimab.

In March this year, the authoritative medical journal New England Journal of Medicine (NEJM) released positive results for a Phase 3 trial that evaluated nirsevimab, developed by Sanofi and AstraZeneca, is the first long-acting monoclonal antibody under development that can provide preventive protection of respiratory syncytial virus for all babies with only one dose.

data showed that nirsevimab reduced the rate of treatment-induced LRTI (including hospitalization) by 74.5% compared with placebo. This data shows that nirsevimab will be expected to provide safe and effective respiratory syncytial virus immune protection for all infants, filling the gap in this field of virus prevention and control.

Currently, nirsevimab has conducted clinical research in more than 30 countries around the world and has been included in the accelerated development qualification of multiple authoritative regulatory agencies. Triomphe introduced, "In China, this prevention plan has not only been included in the breakthrough therapeutic drug procedure by the Review Center of the China Medical Products Administration, but also the third phase clinical research on healthy infants in China has been launched." There is currently no effective drug for preventing and treating respiratory syncytial virus-related diseases in China.

Triomphe concluded that there are many factors that affect vaccine success during the research and development process, "but experience in the pandemic has shown that when we prioritize disease prevention and continuously increase investment in innovation, we can always find ways to solve major public health challenges."

Triomphe also reminded that under the COVID-19 pandemic, we need to be alert to the risks of "immunization programs" or being broken in other infectious diseases.

He emphasized that many infectious diseases with high coverage of basic immunity are also highly contagious and pathogenic. Taking whooping cough as an example, since the diphtheria and tetanus vaccine was widely used in clinical practice in the early 1970s, whooping cough has been effectively controlled. "In recent years, due to factors such as insufficient durability of vaccine immunity or untimely vaccination, differences in vaccination immunization strategies, improvement of diagnostic standards and improvement of monitoring systems, many countries have experienced the phenomenon of "pertussis reappearance". On the one hand, the existing immunization strategies need to be improved. On the other hand, once basic vaccines such as diphtheria and tetanus cannot be vaccinated in time, children will be placed at the risk of infection again."

Another example is the influenza vaccine. In fact, during the peak of the new crown epidemic, most areas around the world were strictly quarantine measures, and influenza was also at a low level. Triomphe believes that this also reduces the pre-existing immunity of the population, which may lay hidden dangers for a new round of influenza outbreak. In addition, many regions have lifted social restrictions, which will easily lead to more serious influenza outbreaks in the future. "So it is crucial to get influenza vaccine before the arrival of the flu season every year."

It is worth noting that in addition to unmet diseases and new technology platforms, Sanofi's vaccine innovation chain also extends to the EVF (Evolutive Vaccines Facilities) factory that promotes the vaccine production revolution.

In summary, EVF uses digitalization to empower vaccine production. “Aim to achieve more agile and flexible production across multiple vaccine and biological platforms, including enzymes and monoclonal antibodies, and minimize our environmental impact. EVF can produce multiple vaccine components simultaneously, both for single-variety vaccines and for more complex combined vaccines."Triomphe introduced that Sanofi invested 900 million euros to build two EVF factories within five years, one in Neuvern on the Thorne in France and the other in Singapore, which is expected to be completed by the end of 2025 and early 2026 respectively.

Triomphe believes that EVF factories have more potential to accelerate capacity expansion and adapt to changes in global vaccine demand. For example, it said that in the past, each vaccine factory usually focused on a certain disease and created its own technology or process. If it switched from one vaccine to the production of another, it would generally take several months to adjust. "With the EVF factory, it only takes about 12 days. "

shortens the "time difference" of vaccines in the Chinese market

For any industry, the Chinese market cannot be ignored. This is no exception to Sanofi. Judging from Sanofi's 2021 financial report, the revenue of China was 2.72 billion euros, and increased by 7.9% year-on-year.

This year also happens to be the 40th anniversary of Sanofi's entry into China. From the perspective of immunization, "we have witnessed the gratifying changes in China's immunization. "China has implemented the national immunization plan since 1978, and the 2007 national immunization plan has expanded its scope from "4 vaccines to prevent 6 diseases" to "14 vaccines to prevent 15 diseases". These include hepatitis B vaccine, BCG vaccine, inactivated polio vaccine, live polio attenuated vaccine, diphtheria and tetanus vaccine, etc.

In Triomphe's observation, on the one hand, the scope of China's immunization plan is constantly expanding; on the other hand, for diseases and vaccines that are not included in the immunization plan, various places in China are also exploring and trying. "For example, since 2007 and 2017, local government financed the elderly and primary and secondary school students for free vaccination, and some cities encourage young women of appropriate age to receive HPV vaccine. "These measures will effectively increase the vaccination rate of susceptible populations and have a positive impact on the overall prevention and protection of Chinese society.

" Sanofi regards China as one of the important strategic markets. We will continue to bring cutting-edge disease prevention solutions to the Chinese public through multi-dimensional vaccine innovation initiatives. "Triomphe said, "We hope to meet the diverse health needs of Chinese people and shorten the 'time difference' of vaccines by accelerating the introduction of innovative technologies and prevention means; in addition, we will continue to increase investment in China, promote the innovation and upgrading of vaccines throughout the entire chain, and help the development of China's public health. "

still takes influenza as an example. Compared with developed countries, the annual influenza vaccination rate of the entire population in China is extremely low, less than 5%. Research on of the Chinese Center for Disease Control and Prevention also shows that the influenza vaccination rate of the elderly over 60 years old is only 4.3%, and medical staff is less than 15%. The WHO's suggestion is that countries will set the target of the influenza vaccination rate of the recommended elderly population to be 75%, and China obviously has a big gap at present.

Triomphe believes that China's low vaccination rate may have many reasons: for example, there is room for improvement in the adult vaccination service system, the traditional technical route vaccine production cycle is long, and the public lacks understanding of the harm of influenza and the value of vaccines.

Triomphe believes that China's low vaccination rate may be due to many reasons: for example, there is room for improvement in the adult vaccination service system, the traditional technical route vaccine production cycle is relatively long, and the public lacks understanding of the harm of influenza and the value of vaccines. html l1

Triomphe said that in the future, Sanofi's multi-dimensional vaccine innovation measures in the Chinese market include, first, committed to accelerating the introduction of more innovative technologies and prevention means. For example, it is expected to become the world's first immune prevention program that can be widely used in infants and young children to prevent respiratory syncytial virus infection, and the world's first approved recombinant quadrivalent influenza vaccine, etc.

Second, promote the construction of China's public health capacity. "Sanofi is also actively seeking cooperation with institutions such as Chinese Preventive Medicine , Peking University , etc., jointly explore new ideas for prevention and immunity, further improve the professional capabilities of medical personnel, help China's public health professional capabilities improve and system upgrade, and improve the detection capabilities of respiratory infectious diseases. "

Third, actively drive innovation in the entire chain of China's vaccine industry. "We continue to promote cooperative innovation between production, education, research and application, and work with all walks of life to seek the best solution for vaccine innovation with an active and innovative attitude. "Triomphe gave an example. This includes cooperating with partners, strengthening public education on digital vaccine science popularization, exploring innovative vaccination solutions such as unmanned vaccination pods, and helping to improve the accessibility of vaccines.

fourth, will continue to actively participate in the construction of Guangdong-Hong Kong-Macao Greater Bay Area and promote the implementation of a number of innovative measures. Including creating a model for China's urban immunization planning strategy, building an international academic exchange platform for high-standard vaccines, and continuing to build an international vaccine innovation center in the Greater Bay Area.

It is worth mentioning that on November 6, 2019, under the witness of the heads of state of China and France, the Shenzhen Municipal Government and Sanofi signed the "Memorandum of Understanding on Strategic Cooperation for Vaccine Innovation" at the Great Hall of the People in Beijing. Both sides will give full play to their respective comparative advantages and jointly promote the vaccine innovation strategic cooperation project. According to the Memorandum of Understanding, Sanofi plans to further increase investment in the next 10 years to promote its vaccine innovation projects, pilot vaccine government-enterprise cooperation mechanisms, create a model for China's urban immunization planning strategy, establish a vaccine innovation center, and create a high-level international vaccine summit forum.

Two years later, on December 4, 2021, the Greater Bay Area International Vaccine Innovation Center was completed in Shenzhen. Triomphe said, "As China's first international vaccine innovation center, its birth is also a very innovative measure at the global level, building a bridge for China's cooperation with global vaccine innovation."

Triomphe commented that China's immunization planning policy has achieved remarkable achievements, "The most direct evidence lies in the extension of life expectancy per capita and the decline in the prevalence of various diseases." From polio that seriously threatens the health of Chinese children to the prevention of diseases such as whooping cough and hepatitis B, it all proves China's determination to prevent epidemic prevention and overall level."

"One point prevention is better than a lot of treatment. The value of vaccines lies not only in its prevention of a specific disease, but also in its positive and long-term impact on individuals, families, and society." Triomphe finally said this.

Editor in charge: Li Yuequn

Proofreading: Zhang Yan