This article comes from the WeChat public account: The Gates Foundation (ID: gatesfoundation) , author: Lee Snow, Word problems from: vision China

I have entered my sixth year at the Gates Foundation. One of the feelings of the past few years is that although Bill Gates ’s name is a household name, most people do n’t know what the Gates Foundation does, why, and how.

The reason is actually very simple. In the 20 years since the foundation was established, what it has done has been very “unpopular” and “marginal”: prevention and control of infectious diseases in low- and middle-income countries (AIDS, tuberculosis, malaria, neglected tropical diseases) , research and development and innovation of vaccines, drugs and diagnostic tools to reduce poverty and development.

A “golden thread” that runs through health and poverty reduction is the vaccine. The foundation was established in 2000. The first donation was a donation of US $ 750 million, and jointly participated in the establishment of the Global Immunization Vaccine Alliance (Gavi) / span> Such a new type of international organization. In 2017, the Gates Foundation co-sponsored the establishment of the Epidemic Prevention Innovation Alliance (CEPI) to support the development of vaccines against pandemics.

Because of the new crown epidemic, vaccine development has suddenly become a global focus. On the one hand, it seems that we should be happy, and the work we support suddenly received huge attention; on the other hand, no one can be happy in the face of the epidemic. Especially in some areas where the new crown was once “eradicated” recently, new cases have been found and re-administration measures have been taken, indicating that before the group immunization is achieved through vaccines, society is rarely peaceful. From a global perspective, due to the extremely strong spreading ability of the new coronavirus, human society can only be immunized in all corners of the worldReally safe.

So I want to talk to you today about when the new crown vaccine will come out, and, how far it will be until it can control the epidemic.

When will the new crown vaccine come out?

It may take 18 months, but this is already very fast.

The development of a vaccine chain is very long. It usually takes 8 to 17 years from preclinical research to final marketing. Even the shortest time to develop the mumps vaccine before it took almost five years to get from the virus sample to the market eligibility step.

Compared with traditional vaccines, the development of this new crown vaccine can be described as “quick speed”. After just a few months of research, there are currently four vaccines in Phase II, three in Phase I and II, and two in Phase I trials. Among the “first units” of these nine vaccines, five were developed by Chinese manufacturers.

Comparison of R & D time between New Crown Vaccine and Traditional Vaccine Source: New England Journal of Medicine

The reason why the new crown vaccine is expected to be available within 18 months is because every link of research and development is driving on the “fast lane”.

In the pre-clinical sequencing link, China announced the COVID-19 gene sequencing information within two weeks after notifying WHO of the epidemic, which is better than atypical pneumonia (SARS) published the sequencing results 10 times faster than the Middle East Respiratory Syndrome (MERS) 4 times.

On January 13, only three days after the new crown sequencing results were announced, the National Institute of Allergy and Infectious Diseases (NIAID) based on the messenger The ribonucleic acid (mRNA) technology produced viral gene samples and handed them over to Moderna, which immediately made the first new crown candidate vaccine.

In clinical trials, Moderna and Conxino ’s new crown vaccines took only 66 days from obtaining viral gene samples to entering the clinic, which is less than the previous “world record holder” Zika (Zika) The 190 days of the vaccine shortened the time by about two thirds.

WHO said at the regular press conference on new coronary pneumonia held two days ago that more than 120 candidate vaccines are currently under development, and the actual number is definitely more, some of which are undergoing clinical evaluation.

Behind the “speed” is technological progress and the result of global cooperation. The new mRNA vaccine technology only needs the results of viral gene sequencing to generate candidate vaccines. This greatly improves the efficiency of the preliminary development of the vaccine. However, due to the difficulty of technology development and the high cost, no manufacturer was willing to invest in it.

CEPI has funded the development of mRNA vaccine technology in the past few years, which also allows this technology to be applied early in this outbreak. After the outbreak of the new crown, CEPI funded four vaccine development projects for the first time, including Moderna’s vaccine. As of May 11, it has expanded to 9 projects with a scale of 448 million USD.

Projects funded by CEPI must promise that the research results will be inclusive globally and not exclusive to individual countries, which guarantees the fair and accessible future of the vaccine from the source of scientific research.

Similarly, in order to support the scientific research work of the outbreak, WHO established the R & D blueprint mechanism (R & D Blueprint) in 2016, not only It supports the formulation of clinical trial standards in epidemic situations, and also includes the selection of priority directions and pathogens for R & D, design of R & D paths, and product target characteristics. With the R & D blueprint, scientists can better under the guidance of industry experts and WHO ’s comprehensive coordinationConduct compliance research on priority issues.

Can the vaccine control the outbreak?

In fact, there is still a long way to go. Successfully developing a safe and effective vaccine is only the first step in the long march of the “anti-epidemic road” .

With the vaccine, if you want to achieve global immunization faster and more efficiently, there are extremely complex vaccine delivery issues that need to be coordinated and resolved, from production capacity to price, to the admission and vaccination projects in various countries. So how to mass-produce the new crown vaccine and inclusive the world is now a problem that must be considered.

Global vaccination is the only way to achieve human immunity to the new crown. Ideally, people in all countries should have the opportunity to get vaccinated. However, it is not difficult to imagine that no matter which country takes the lead in producing vaccines, it will face the pressure of giving priority to meeting its own needs. But if the leading vaccine research and development countries all follow the principle of national priority, the results may be disastrous for global public health.

Because the equitable distribution of vaccines is not just about humanitarianism, it is also about meeting the needs of global public health.

No matter how it is prepared in the early stage, the vaccine will not be able to cover the world at the beginning of its birth. To control the global epidemic as soon as possible, who should be given priority in the short term? This is not a problem that market bidding can solve. It requires global public health experts to plan and coordinate.

The question of who should be given priority is currently inconclusive, but several types of people deserve special attention. The first is the susceptible group headed by medical personnel, who are the closest to the virus; the second is the group that is prone to cause super-spread incidents, such as group accommodation employees, teachers, students, prisoners and practitioners who contact a large number of people; Employees, society cannot operate without them; and the elderly and people over the age of 65 and patients with basic diseases, this is the most vulnerable group facing the new crown epidemic, the risk of serious illness, complications, and death after infection is high, requiring special protection. The priority inoculation sequence defined by this principle will transcend national borders, reduce the death and cost of the new crown as much as possible, and accelerate the return of society to normal.

Looking around the world, low-income countries are most affected by the new crown epidemic and are “losing” in a dangerous way. The poorer countries have worse health conditions. The lack of clean water and basic medical facilities are the survival difficulties faced by the poor, plus their jobs are difficult to transfer online, so once they are segregated, they will face wage cuts and unemployment. These three factors alone have greatly increased their suffering. The possibility of death due to virus infection.

In addition to the direct health effects of infectious diseases, poor people are also facing worsening of malnutrition, food shortage, long-term unemployment, and homelessness in the epidemic. According to estimates by the United Nations World Food Program, 1 billion people in low- and middle-income countries are currently hungry, and the number of severely hungry people in the world may double by the end of the year. The United Nations Development Programme even predicted that the outbreak might destroy half of Africa ’s work.

Therefore, if low-income countries are ignored in the distribution of vaccines, allowing the epidemic to continue will likely lead to a global humanitarian crisis, with irreversible consequences.

African countries are facing severe food shortages Source: BBC

Influenza A H1N1 in 2009 is an example worthy of reflection. At the time, the researchers made a new flu vaccine in only six months, but almost all supplies were monopolized by developed countries. Vaccine manufacturers eventually donated a small portion of the vaccine to WHO, but the magnitude was too small, and H1N1 caused 18,000 deaths worldwide. The New Crown epidemic is more terrifying than H1N1 in many ways-more spreading and lethal, and has a greater impact on the economy and society. If the scene of the 2009 H1N1 vaccine repeats itself, the world ’s losses will be even more severe.

In the long run, achieving group immunization of the new crown requires universal vaccination, which means the production capacity of billions of vaccines. The construction of new vaccine plants often requires hundreds of millions of dollars and takes several months. If large-scale production of new vaccines is to be produced within 12 to 18 months, investment in the construction and transformation of vaccine plants needs to start now.

However, this is not easy.

Because it is currently unclear which technology will successfully test, and different vaccine technologies have different requirements on the plant. Inactivated vaccines are very common in the market, but due to challenges such as the production of biosafety level 3 standard factories, there are not many companies that develop inactivated vaccines worldwide. In contrast, the production of mRNA vaccines depends on the preparation of nucleic acid molecules, which is characterized by rapid and large-scale production, but due to the relatively new technology, there is no corresponding production facility, technical personnel and quality control process, and ultra-low temperature cold chain Transportation is difficult to meet global demand. Other vaccines, such as subunit vaccines, require adjuvants to help improve the immune effect. In the case of limited adjuvant production, vaccine production has obvious bottlenecks.

In the case of uncertain technical prospects and limited production capacity of each technical route, the most reliable way may be to allocate capacity for multiple technical routes in advance. Otherwise, countries will face the embarrassment of successfully developing vaccines but spending months waiting for production.

Who pays for low-income countries?

To ensure fair access to vaccines, huge amounts of capital and sufficient production capacity are required, and these require a set of effective mechanisms to achieve.

Here we will talk about the (Gavi) organization that we mentioned earlier. Under the initiative of the World Bank, WHO, UNICEF (UNICEF) , Gates Foundation and governments, Gavi was founded in 2000 Established to purchase vaccines at low prices for children in poor countries.

On the one hand, by integrating the needs of multiple poor countries, a scale effect is formed to ensure their bargaining power with predictable and relatively large demand; on the other hand, the long-term commitment of the donor country to the production enterprises Provide guarantees to reduce the investment risk and production costs of enterprises, and encourage enterprises to continue production and R & D. Over the past 20 years, Gavi has supported 496 vaccine projects in 73 of the poorest countries, and has vaccinated more than 760 million children, reducing the deaths of more than 13 million children.

When the international community needs to come up with “eighteen martial arts” to counter the menacing outbreak, it is also particularly important to innovate effective financing tools.

In 2007, Gavi passed the “Advance Market Commitment” (Advance Market Commitment) with $ 1.5 billion in funding from the Gates Foundation and five national governments way to place orders with pharmaceutical companies, 73 lowIncome countries continue to purchase pneumonia vaccines. Because of its good credit and long-term large orders, Gavi has a strong bargaining power when purchasing vaccines, which can often reduce the price of vaccines by dozens of times, making large-scale vaccination of vaccines in poor countries economically feasible. As you can see from the chart below, the US $ 1100 vaccine Gavi can talk about the US $ 27 purchase price.

Gavi ’s integration of the needs of poor countries has greatly reduced the purchase price Source: Gavi

In addition, Gavi has been financing “vaccine bonds” in the capital market since 2006. With the aid of the “International Finance Facility for Immunisation”, also known as “IFFIm”, Gavi’s vaccine debt is borrowed in the capital market, and behind it are payment commitments from governments. Competitive interest rates and the use of solving world problems have made vaccine debt a popular financial product in the capital market.

These proven mechanisms can also be used to ensure the fair access of the new crown vaccine. According to Gavi’s prediction, at the beginning of the birth of the new crown vaccine, an investment of US $ 2 billion will be needed to provide vaccines to 20 million medical workers, establish a strategic material database to respond to sudden outbreaks, and provide immunization to high-priority groups. Compared with the billions of dollars of economic losses caused by the epidemic every day, this sum is not much.

Gavi has proposed a “pre-market commitment” mechanism that promises to purchase large quantities of vaccines at a fair price to encourage manufacturers to invest in large-scale production; at the same time, through innovative financing methods including “vaccine bonds”, to expand production Ability to provide funding, ensure the supply of key raw materials and equipment, and help achieve vaccine technology transfer, thereby accelerating the realization of fair access to vaccines.

Since the new crown epidemic, multilateral organizations and various governments are also taking active actions. On April 24, WHO and global partners jointly issued the “Global Cooperation to Accelerate Development, Production,From a perspective, the significance of the new crown vaccine is not only to save people, but also to restore the global political and economic order and fill the social rifts caused by the epidemic.

The Gates Foundation was established 20 years this year. The institutions and mechanisms behind the entire vaccine chain mentioned in the article can be proudly said that most of them are related to the work of the Foundation, and many can be said to be because the work of the Foundation has become a reality. There are actually a lot of breakthroughs and innovations in mechanism, not just technology and products.

I think this is why the Foundation is paying attention to these “cold areas”. Because first, these areas are actually related to the well-being of most people on our planet. The new crown reminds us of this in a tragic form; second, in these areas, we actually need innovative and cooperative thinking.

I think this time, we should all do better.


[1] Ault, Alicia. Equitable Vaccine Distribution Key to Stopping COVID-19, Experts Say. 26th April 2020. May 2020. .

[2] Bank, Asian Development. COVID-19 Economic Impact Could Reach $ 8.8 Trillion Globally — New ADB Report. 15th May 2020. May 2020. .

[3] Blume, Stuart. Get Ready for the Global Fight Over Vaccin