Construction of China's Strategic Science and Technology Forces from Research and Development of COVID-19 Vaccine

A report at the 19th National Congress of the Communist Party of China (CPC) suggests to strengthen the construction of innovation system and reinforce strategic science and technology forces of China. National strategic science and technology forces embody state will, shoulder state mission, and stand for national science and technology level. Strengthening strategic science and technology forces is the key to achieving scientific and technological self-reliance and self-improvement. The research and development (R&D) of COVID-19 vaccine hinges on national strategic science and technology forces. In light of the status quo of COVID-19 vaccine R&D, we find it essential to review its path, experience, and strategies. Attributed to governmental responsibilities and the exercise of market economy in the context of global pandemic, China has reaped phased achievements in COVID-19 vaccine R&D, in which national strategic science and technology forces play a critical role. The research on it will shed light on how to improve China’s strategic science and technology forces.

The R&D status quo of COVID-19 vaccine

Global overview

Vaccine is considered as the most effective and economical means to prevent and control a pandemic. After the outbreak of COVID-19, countries around the world are urgent to develop safe and effective vaccines as soon as possible. According to the data released by World Health Organization (WHO), as of May 25, 2021, a total of 101 COVID-19 vaccines have entered clinic trial stage, including 36 recombinant protein subunit vaccines [including peptide vaccines and virus-like particle (VLP) vaccines], 26 nuclear acid vaccines (DNA vaccines and RNA vaccines), 18 viral vector vaccines, 16 inactivated vaccines, and two live attenuated vaccines. So far, 12 COVID-19 vaccines have been registered for being launched to the market or have been launched to the market with conditions in many countries. Large-scale vaccination has been initiated, being an important approach to curbing the spread of COVID-19.

1.2　China’s overview

China is one of the few countries capable of independently developing vaccines for the immunization program. In the face of COVID-19, China took the lead in vaccine development relying on science and technology. China is making good use of its new system concentrating nationwide efforts and resources on key undertakings, showing to the world China’s sharp competitive edge in the global vaccine race. In January, 2020, China launched R&D projects to tackle emergence problems including vaccine development. Regarding vaccine development, China has deployed five major technological lines with 12 selected research teams. As of April, 2021, a total of 19 vaccines across the country have been approved for clinical research, covering all the five technological lines. National Vaccine and Serum Institute, Wuhan Institute of Biological Products Co., Ltd., and Sinovac Research & Development Co., Ltd. developed inactivated vaccines, respectively. Academy of Military Medical Sciences and CanSinoBIO jointly developed an adenovirus vector vaccine. All of the above vaccines have been approved for marketing conditionally. The Institute of Microbiology, Chinese Academy of Sciences (CAS) and Anhui Zhifei Longcom Biopharmaceutical Co., Ltd. jointly developed a recombinant COVID-19 vaccine, which was approved domestically for emergency in March, 2021.

The speed from initiation to approval has far outpaced the regular duration of 5–18 years and surpassed that of 12–18 months in the context of a pandemic. China ranks top in terms of COVID-19 vaccine quantity, category, and R&D speed.

China’s experience in R&D of COVID-19 vaccine

China’s success in COVID-19 vaccine R&D illustrates China’s new system concentrating nationwide efforts and resources in response to emergence, which has built up experience in using science and technology to underpin national major strategies.

Coordinated arrangement facilitates the concentration of nationwide efforts and resources

COVID-19 vaccine R&D is a typical example showing how China responds to emergence through a new system concentrating nationwide efforts and resources on key undertakings. This new system is vital to the success in COVID-19 vaccine R&D and provides institutional guarantee for the strengthening of strategic science and technology forces.

(1) The CPC Central Committee makes wise decisions. Gaining insights into the strategic value of COVID-19, the CPC Central Committee places people’s life and health in priority. Upon the outbreak of the pandemic, China has made concerted efforts by making full use of all available resources and intensified the investment in vaccine R&D. China has launched a state-level vaccine reserve project and promised to make COVID-19 vaccines global public products, which offers COVID-19 vaccine producers ample market space.

(2) The deployment is scientific and adopts parallel lines. The Research Group for Joint Prevention and Control of COVID-19 under the State Council (hereafter referred to as the Research Group) treated vaccine R&D as its prioritized task. Through screening, it confirmed the synchronous promotion of the R&D in inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, vaccines using attenuated influenza virus as vectors, nuclear acid vaccine. The links and stages of vaccine R&D which used to be in series are now in parallel, which greatly shortens the needed time.

(3) Resources of all parties are organized to form joint forces. Under the leadership of the CPC Central Committee, the Research Group coordinates the vaccine R&D process. Relevant departments work together to ensure that science and technology resources, policy examination and approval, and materials are available to meet the needs of key tasks.

① Vaccine R&D. The forces of research institutions, medical institutions, and enterprises are assembled to integrate laboratory R&D, animal experiments, pilot scale production, and clinical trials. ② Vaccine production. China simultaneously promotes R&D and production. Multi-departments work together to speed up the examination and approval of the facility construction for vaccine production, strengthen vaccine production scheduling, and expedite enterprises’ productivity building, so as to stabilize production, industrial chain, and supply chain in preparation for large-scale production. ③ Vaccine evaluation and approval. China innovates vaccine evaluation and approval patterns. Regulators step in early to guarantee interconnection between vaccine R&D and approval. The government, research institutions, approval authorities, and enterprises coordinate with each other to maximize the efficiency and success rate of vaccine R&D. R&D is a long-term process, in which universities, research institutions, and enterprises draw on each other’s strengths.

Universities, research institutions, and enterprises draw on each other’s strengths in the long-term R&D

China’s success in the rapid development of COVID-19 vaccines is attributed to its long-term independent innovation in bio-medicine. The long-term development of science and technology lays a foundation for the successful R&D of COVID-19 vaccines. Moreover, it underpins the development of China’s strategic science and technology forces.

(1) China’s innovative R&D capacity of vaccines has improved significantly. China has greatly improved its innovation capacity for vaccine R&D owing to the state’s years’ support for science and technology development, especially the major project “Key Technology for Vaccine Research and Development and Product Development” under National High-tech R&D Program (863 Program), National Science and Technology Major Projects “Prevention and Treatment of Serious Infectious Diseases such as AIDS and Viral Hepatitis” and “Formulation of Major New Medicines”, and National Key R&D Program “Research and Development of Key Technology for Biological Security.” China is the first to succeed in developing recombinant hepatitis E vaccine, inactivated enterovirus 71 vaccine, recombinant Ebola virus vaccine, achieving good social benefits and economic efficiency. China’s experience in technology development, talent training and reserve, platform establishment and development, research team building in its fight against bird flu and H1N1 influenza has laid a solid foundation for China’s R&D of COVID-19 vaccines.

(2) China’s strategic science and technology forces play an important role in emergency response. The 12 COVID-19 vaccine R&D teams selected by the Research Group are mostly the national strategic science and technology forces long supported by national science and technology programs. ① Research institutions serve as the backbone. The CAS, the Academy of Military Medical Sciences, the Chinese Academy of Medical Sciences and many other research institutions provide general technological support through multidisciplinary platforms such as virus isolation, antigen design, animal modeling, in vivo and in vitro evaluation, and quality evaluation. The rapid application of research results to vaccine R&D has enabled China to spearhead the R&D of COVID-19 vaccines around the world. ② Major science and technology enterprises play a key role. Vaccine producers with rich R&D experience and complete technology industrialization platforms have made great contributions. With their own superiority in technology or production, these enterprises invest in advance in vaccine R&D and expand their production capacity during the pandemic. They shoulder their due corporate social responsibilities.

(3) Universities, research institutions, and enterprises collaborate to draw on each other’s strengths. An important approach to the R&D of COVID-19 vaccines is to enhance the cooperation between universities, research institutions, and enterprises. Such cooperation can break the “last-mile” bottleneck of industrialized R&D of COVID-19 vaccine. Thus, it shapes a seamless joint pattern, in which the government steers the direction, national strategic science and technology forces act the main players, and enterprises are ready to approach government, universities, and institutions. Successful cases include but are not limited to the followings. The Academy of Military Medical Sciences and CanSinoBIO, based on their long-term cooperation, have jointly developed adenovirus vector vaccines, which is the first COVID-19 vaccine entering the clinical stage. The CAS and Anhui Zhifei Longcom Biopharmaceutical Co. Ltd jointly developed a recombinant COVID-19 vaccine, which is the first recombinant protein vaccine against COVID-19 approved for use in the world.

Demand-driven and objective-oriented R&D

The COVID-19 vaccine R&D aims to meet national major strategic demands. It encompasses basic research, key common technologies, and production. China has developed a successful paradigm for COVID-19 vaccine R&D, which is demand-driven and objective-oriented. Such paradigm sparks ideas for building up national strategic science and technology forces.

The COVID-19 vaccine R&D embodies the evolution and development of Pasteur’s quadrant theory in China which pools its resources to realize the goal. To control the pandemic of COVID-19, China rallies all its forces to focus on prevention and control technology and vaccine R&D. In the course, China identifies problems and develops new understandings. New insights drive China to tackle strangling problems in vaccine R&D to address critical issues in prevention and control technology and products.

(1) Immediately identifying COVID-19 vaccine application as the research objective. First, China confirms applicable COVID-19 vaccine types and reachable capacity. Second, top-level design and decomposed deployment are put in place. ① To maximize the success of COVID-19 vaccine R&D, China sets in advance multiple technological routes in parallel and promoted a holistic R&D strategy. In light of the success possibility of different technological routes and China’s domestic existing conditions, China

finalized five major technological routes, and supported a total of 12 research teams for emergency research. ② In line with reachable capacity and institution–enterprise integration principle, China initiated, in advance, production facility construction, trial production, and raw material reserve to guarantee productivity expansion.

(2) Spotting new science-related issues in the COVID-19 vaccine R&D. Aiming at antigen design, efficacy and safety evaluation of candidate vaccines, process development, quality control and verification, clinical trials and large-scale production, the Research Group dynamically track and collect the feedback data to punctually spot the science-related issues to be urgently addressed. Is the choice of COVID-19 vaccine antigens immunogenic and specific enough to handle viral mutations, and to elicit durable immune response? In terms of vaccine safety evaluation, will candidate COVID-19 vaccines cause acute toxicity and repeated toxicity, and how can we predict and prevent the antibody-dependent enhancement (ADE) of COVID-19 vaccines? In terms of vaccine efficacy evaluation in clinical trials, how can human responses be better predicted via animal models? Are humoral and cellular immunity stimulated by COVID-19 vaccines equally important? And is it possible to establish surrogate endpoints for COVID-19 vaccine efficacy ‌evaluation?

(3) Concentrating efforts and resources to tackle critical problems. Having identified science problems, the research teams conducted research centered on the screening and optimization of antigen and the prediction of ADE. On one hand, to address these science problems, we need to further improve basic research of virology, immunology, and vaccinology. On the other hand, solving these problems will not only support the optimization and innovation of COVID-19 vaccines but also provide new targets for the development of antivirals and new ideas for blocking the spread of the virus.

Reflection on China’s strategic science and technology forces

The R&D of COVID-19 vaccine sheds new light on the building of China’s strategic science and technology forces. The 19th National Congress of the CPC, and the Fourth and Fifth Plenary Sessions of the 19th CPC Central Committee have made an overall action plan for strengthening national strategic science and technology forces. It has become an extremely important task for building China’s science and technology innovation system. To this end, we need to explore the organization mode, function positioning, and operation mechanism.

Mission positioning: combination of long-term and emergency missions

China’s experience in the prevention and control of COVID-19 shows that a country should make forward-‌looking technological deployment in advance, accumulate adequate research experience, build up technological reserve, and set definite national science and technology positioning and fully-fledged emergency response mechanism. To accurately position national strategic science and technology forces, we must take into account both long-term effect and the need for emergency. For one thing, we must ensure that the positioning is visionary, lasts long, and can produce a permanent effect. For another thing, it should meet the demand, especially emergency and even potential risks. We must make discipline, domain, and territory arrangement conform to the country’s medium-to-long-term planning. We encourage original innovation to underpin China’s efforts to build itself into a strong country to lead science and technology in the future. Supported by strong R&D and industrialization capacity, we should maximize strong points and give full play to grouping competitiveness to gear to the need of national major strategies. We should bring science and technology into play to deal with “black swan” and “grey rhino” events.

Top-level design for regular and emergency purposes

To organize and motivate quality forces from across the country for science and technology innovation in pandemic prevention and control, the Research Group sets a special group responsible for virus isolation, animal experiment, product preparation, and clinical research. China’s promotion of COVID-19 vaccine R&D observes the laws of science. The special group for vaccine R&D is a well-coordinated measure in response to emergency. It is only through close and effective coordination that national strategic science and technology forces from different domains can pool resources to accomplish sizable tasks. Such coordination mechanism should serve both emergent and regular purposes under the guidance of relevant governmental authorities.

In case of no emergency, we should observe the laws of science. Considering the major tasks and goals of science and technology innovation, we should make continuous efforts for technological reserve and talent building in a regular manner. We must foster national strategic science and technology forces through

institutionalization. Meanwhile, we should, step by step, set up a regular coordination mechanism to improve the research team and capacity building to guard ourselves against public health emergencies.

Strengthening methods: with focus on both reorganization and empowerment

In terms of current policy design and practice, reorganization and empowerment are two effective paths available. Sticking to the principle of inheriting fine tradition and seeking innovation, we should handle well the relations between reorganization and empowerment, as well as between increment and stock in organizational structure and developmental mechanism. (1) Ensuring quality and increment through reorganization. Various innovation players should be organically regrouped in biological technology and life science which are interdisciplinary, intensive, and collaborative to enable state-level labs and large-scale innovation enterprises to break new ground and achieve new inventions.

(2) Invigorating key science and technology forces. Taking into account the big picture of a national innovation system, we must coordinate science and technology innovation forces, improve element allocation, and systematically build a talent group for state-level science institutes and major universities to enable them to make fresh contributions and ‌accomplishments.

Policy suggestions

The world is undergoing profound changes unseen in a century. We must take into full account the profound adjustment of international competition in economy as well as science and technology, and seize the strategic opportunity of a new round of scientific and industrial revolution. We should uphold Xi Jinping’s Thought on Socialism with Chinese Characteristics for a New Era as the theoretical and practical guidance. Efforts should be made to improve the top-level design for national strategic science and technology forces and the innovation ecology. It is suggested to sharpen the competitiveness of national strategic science and technology forces through original innovation. Such initiative is driven by national major tasks and demands. We must make good use of the new system concentrating nationwide efforts and resources on key undertakings to reinforce national strategic science and technology forces.

Systematic deployment and forward-looking planning

(1) Strategically valuing top-level design. ① In terms of strategic direction, we must give full play to the role of the state in organizing major science and technology innovations. All we do must aim to meet the strategic demand of national major strategies and put people’s life and health on the top position. ② The endeavor needs to be driven by well-defined strategic tasks geared to global advance level, economic development, national major demand, and people’s life and health. We set biotechnology and life and health as the new orientations and focuses of innovation. Priority should be given to addressing critical problems limiting science development and national security. ③ We should continue to build high-level R&D platforms. Relying on research institutions, universities, and key enterprises, we should strengthen the construction of new R&D institutions in the basic, frontier, emerging, crossing, marginal disciplines, and weak and vacant disciplines of life sciences and biotechnology, and focus on cultivating the reserve team of national key laboratories in these fields. ④ In terms of team building, we will steadily support a number of research teams shouldering the national missions, and introduce and cultivate top-notch scholars and innovative teams meeting the standard of national strategic science and technology forces. We should improve the assessment and evaluation system, which should uphold research quality and academic contribution and focus on the originality, contribution, and impact of research achievements.

(2) Dual-wheel driving tactic. According to the development trend of global life and health, we should maintain strategic focus and vision, and adhere to the dual-wheel drive of technological innovation and institutional innovation. The allocation of resources and the layout of innovation factors should be optimized. Specifically, resources in key technology areas to be prioritized should be concentrated to highlight competitive advantages. We should strengthen the coordination of national strategic technological forces and market players to accelerate the transfer and transformation of technological achievements and facilitate the key links of the innovation value chain.

Far vision and pragmatic attitude

(1) Conducting in-depth basic and applied research geared to the need of the future. We should support autonomous basic research and establish a stable support initiative that conforms to the law of basic research. The top teams of national strategic technology forces should be given strong and stable support as well as complementary services to engage in research in a worry-free environment. We should enhance our financial support for basic research, forward-looking and non-consensus research to foster disruptive innovations.

(2) Reinforcing national strategic science and technology forces in practice to meet the current demand. Driven by national major demands and significant science and technology tasks, we should provide practical opportunities to strengthen national strategic science and technology forces. By giving full play to state labs, state key labs, regional innovation centers, and science and technology enterprises, which serve as the vehicle of national strategic science and technology forces, we should manage to integrate multiple disciplines and gather top talents at home and abroad to tackle major science issues and core technology. In practice, state-level R&D forces oriented to the future are gradually fostered through an organization system.

(3) Strengthening national strategic science and technology forces by utilizing global innovation resources. While adhering to Chinese characteristics, we should integrate ourselves into the global innovation system. We should grow ourselves into a key node in the innovation network and make good use of global innovation resources to build up national strategic science and technology forces. State-level science institutions are expected to open posts to talents from across the world. We encourage high-caliber science researchers to serve important posts in international organizations to participate in global governance and international standard formulation in science and technology.

Building an innovation system to provide wide-ranging services

(1) Integrating the new system concentrating nationwide efforts and resources on key undertakings into the building of national strategic science and technology forces by providing governmental innovation services. National science and technology departments in charge should endeavor to scale up innovation services. Governmental services should be an element of national strategic science and technology forces. Science management agencies shall play a role in resource integration and organization coordination. We must make sure that the organization and implementation of major science tasks should meet the need of the country and manifest state will.

(2) Realizing resource sharing by building strategic innovation resource reserve and public technology platforms. Efforts should be made to build bases that are for public good, shared, and open, such as platforms for laboratory animal and diseased animal models, standard and evaluation platforms, and state-level biology information center. It is recommended to strategically deploy animal resource, microorganism resource, and human heredity resource reserves. To improve science resource allocation and sharing, we must first guarantee resource supply for national strategic science and technology forces.

(3) Accelerating the commercialization of achievements to optimize innovation ecology. We should regulate the coordinated innovation mechanism for promoting cooperation, establish an active science operation and mobilization mechanism, and set up a supporting system in place. The connection of supervision, access, application institutions with science innovation should be stressed to smooth the chain of policy. A sound supporting institution favorable for talent initiatives, finance and taxation should be built to create the innovation ecology conducive to the commercialization of innovation achievements.

Author

ZHANG Xinmin, Director of China National Center for Biotechnology Development, Ministry of Science and Technology

This article is contributed by Bulletin of Chinese Academy of Sciences.