Beijing reported that “At the moment when the mutants of the new crown epidemic are constantly developing and changing, it is necessary to continuously develop vaccines in response to the needs of the epidemic. We ultimately need a broad-spectrum vaccine for the new crown, so that we don’t have to keep tracking each mutant.” Recently, At an industry discussion meeting, Seth Berkeley, CEO of the Global Alliance for Vaccines and Immunization (Gavi), told the 21st Century Business Herald and other media.

In addition to focusing on the constantly mutating strains, Seth Berkeley is more concerned with the distribution of the new crown vaccine. To address the long-standing inequity and inequality in global health, vaccines are actually a critical global public good. How to further expand vaccines as a global public good and make them accessible to everyone in the world is a major global health issue.

Zheng Zhijie, director of the Department of Global Health at the School of Global Public Health at Peking University and deputy dean of the Institute for Global Health Development, also pointed out that as of June 9, 2022, 75% of the population in high-income countries have completed the full course of the new crown vaccine vaccination, but low More than 80% of the population in income countries are still not vaccinated. To make vaccines a global public good means that different social sectors, such as the public, private and philanthropic sectors, give full play to their respective functions, and work together in the process of vaccine research and development, production and distribution, and continuously innovate and deepen cooperation models and cooperation mechanisms.

Continue to increase investment in vaccine research

Since the outbreak of the new crown epidemic, strain mutation and response have been the focus of attention.

The new coronavirus strain is constantly iterating. In September 2020, the alpha strain (α) of the new coronavirus appeared, followed by the beta strain (β), the gamma strain (γ), etc. In February 2021, the delta strain (δ) appeared and spread rapidly around the world. By November 2021, more than 99% of the submitted genome sequences of the new coronavirus worldwide were the delta strain. In November 2021, it was observed that another mutant strain began to appear, which was also the 15th mutant strain named with Greek letters, named Omicron (ο) mutant strain, becoming the fifth VOC strain, the previous 4 VOC strains. The strain became a historically popular strain.

With the prevalence of Omicron strains, three subtypes emerged, namely BA.1, BA.2 and BA.3. In the early stage of the Omicron epidemic, it was mainly BA.1 and BA.1.1. By the end of January 2022, the popularity of BA.2 gradually increased. Recently, BA.4 and BA.5 subtypes appeared in the Omicron strain. type, also triggered the popularity in some areas.

Seth Berkeley pointed out that tracking the continuous mutation of the virus is not easy. They are circulating in different regions and cause different immune responses, but the good news is that the evidence so far shows that all vaccines are effective in preventing severe illness and death. , which is done at the level of cellular immunity.

“In contrast, at the antibody level, the effect of vaccines in helping us reduce infection or reduce transmission is relatively modest. Therefore, the protection of vaccines against Omicron’s infectivity has declined, leading to a new wave of infections in some countries. If The virus continues to mutate to the point where our current vaccines cannot avoid severe illness and death, then we must invest in new vaccines.” Seth Berkeley pointed out.

Since the outbreak of the new crown epidemic, Professor Jiang Shibo, academician of the American Academy of Microbiology and director of the Institute of Pathogenic Microbiology of Fudan University, has repeatedly emphasized that the new crown virus will mutate in the future. Develop efficient and broad-spectrum universal vaccines and drugs against human coronavirus as soon as possible.

In Seth Berkeley’s view, if a broad-spectrum vaccine is developed that can prevent various strains, or a vaccine that can effectively block the spread of the virus, for example, there are also vaccines that can protect the mucous membranes of the nose and mouth. This may be a better vaccine.

“For any epidemic, it is necessary to continuously develop new vaccines, which is very important for epidemic response.” Zheng Zhijie said that in the future, with the continuous mutation of new coronavirus strains, vaccine research and development will continue to be carried out, in order to solve global health problems , to meet the health needs of more regions. From the perspective of vaccine research and development, nasal vaccines may become the future vaccine stars, and broad-spectrum vaccines will also become important research objects of major R&D teams.

On May 26, 2022, a team from Xiamen University, the University of Hong Kong, Beijing Wantai and the China Institute for Food and Drug Control published an online publication titled “A live attenuated virus-based intranasal COVID-19” in the international academic journal Science Bulletin. 19 “vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2” research results, reports the results of preclinical research and immune mechanism research of nasal spray influenza virus vector new coronary pneumonia vaccine (hereinafter referred to as “nasal spray vaccine”).

The nasal spray influenza virus vector COVID-19 vaccine jointly developed by Xiamen University, Hong Kong University and Beijing Wantai is based on a double attenuated influenza virus vector, which carries the new coronavirus RBD gene and can be inoculated by nasal spray CA4-dNS1 -nCoV-RBD (referred to as dNS1-RBD), is also the world’s first nasal spray preventive vaccine against new coronary pneumonia to enter human clinical trials.

However, the nasal spray vaccine has not been widely developed and used, and little is known about its mechanism of action and immune effect indicators, which makes the research and development of such vaccines face great challenges. The results of this study suggest that the nasal spray influenza virus vector COVID-19 vaccine has good safety and can effectively induce immune responses in adults. At present, the vaccine is undergoing large-scale phase III clinical trials in the Philippines, South Africa, Vietnam, and Colombia to directly verify its protective effect against new coronary pneumonia, in order to form a good complement to the currently widely used intramuscular injection of new coronary pneumonia vaccine and help the global new coronary pneumonia epidemic. prevention and control.

It is also understood that on March 29, Sinopharm Zhongsheng Biotechnology Research Institute/National Engineering Research Center for Novel Vaccines (hereinafter referred to as “China Institute of Biological Research”) published an online preprint platform bioRxiv entitled “A mosaic-type trimeric RBD -based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants” research paper. In view of the high variability of the new coronavirus, the research team innovatively designed a single-component broad-spectrum recombinant new crown vaccine with mosaic trimerized RBD (mos-tri-RBD) as the target antigen. The study focused on the effect of this single-component broad-spectrum recombinant new crown vaccine as a booster. The study found that for Omicron, Beta and Delta variants, the use of this vaccine for heterologous boosting has obvious immune advantages, and the effect is better than Inactivated vaccine boost.

However, in contrast, the development of broad-spectrum vaccines is not easy. The premise of broad-spectrum vaccine design is that the antigen itself has broad-spectrum epitopes. Such epitopes need to be conservative enough and have good immunogenicity. Looking only at the S protein, mutations in the NTD and RBD genes result in major antigenic changes in the S protein. From the new mutants, the RBD tends to have the most variation. There is a lot of variation because of the selection pressure exerted by the immune system. These antibodies are generally very potent and target the first step in viral invasion: the process of binding to receptors. And the virus will try its best to escape. Therefore, it is difficult to achieve a broad spectrum, or can only achieve a very limited broad spectrum.

Addressing vaccine delivery issues remains key

In 2020, the 73rd World Health Assembly made a resolution that in order to completely end the new crown pandemic, the new crown vaccine should be listed as a global public health product, so that everyone around the world can obtain and afford the new crown vaccine. At present, China’s new crown vaccine is also a global public good, contributing to the accessibility and affordability of vaccines in developing countries.

Zheng Zhijie pointed out that China has three new crown vaccines on the WHO emergency use list. By the end of 2021, it has provided more than 2 billion doses of vaccines to the world through bilateral and multilateral channels, most of which have been supplied to developing countries, contributing to the promotion of vaccine equity. strength.

Seth Berkeley also introduced that at present, China has delivered 228 million doses of the new crown vaccine to 50 countries through COVAX (the “New Coronary Pneumonia Vaccine Implementation Plan” jointly initiated by Gavi and the World Health Organization and other multilateral health organizations). These vaccines will play a key role in 2021 when global supplies of Covid-19 vaccines are particularly tight. It is precisely because of the support of donor countries like China and the support of vaccine manufacturers like Sinopharm and Sinopharm that COVAX has now provided 1.5 billion doses of new crown vaccines to 146 countries and regions.

“Our support for low- and middle-income countries has continued to grow, and we have now achieved 54% coverage for the first dose and 47% for the second dose in 92 low- and lower-middle-income countries. There is a lot of work to be done, but significant progress has been made to bring the global average vaccination rate to 60% or 61%.” Seth Berkeley further explained.

According to the 2019 Global Burden of Disease Statistics by the Institute for Health Metrics and Evaluation (IHME) of the University of Washington, the diseases affecting high-income countries are mainly various cancers such as ischemic heart disease, stroke, lung cancer, etc. Chronic, non-communicable diseases. Low-income countries are mainly affected by respiratory diseases, infectious diseases, malaria, AIDS, meningitis, anemia, etc. It can be seen from this that infectious diseases are the main threat faced by less developed countries, which bear almost 90% of the global disease burden.

“In those countries with fragile health care systems, they face the problem of insufficient funds and insufficient medical personnel.” Seth Berkeley pointed out to the 21st Century Business Herald reporter that as of January 2022, 34 countries have not reached 10%. As of June this year, there are still 18 countries where the vaccination rate has not reached 10%, and 14 of the 18 countries are countries with weaker health systems, so COVAX support work is difficult to implement.

Seth Berkeley said that COVAX’s support work in developing countries has been affected to some extent due to the spread of many rumors around the world through social networks, but most people in most African countries are still willing to be vaccinated, and only a small number of people are skeptical about vaccines. The real challenge lies in addressing the delivery of vaccines and supporting the systems involved.

In Zheng Zhijie’s view, making vaccines a global public good and improving regional differences requires different social sectors such as public, private and charitable sectors to fully exert their respective functions and work together in the process of vaccine development, production and distribution. Cooperation. That is, the provision of global public goods requires a series of multilateral cooperation mechanisms as an “infrastructure”. This “infrastructure” is not only “hardware”, but also includes continuous innovation and deepening of cooperation models and cooperation mechanisms.

Previously, Japanese encephalitis was an incurable infectious disease, especially in poor rural areas in Asia and the Western Pacific. Ten years ago, more than 3 billion people worldwide were still at risk of JE. While the JE vaccine is already available, it is expensive to produce and severely under-capacity to protect all of the world’s children in need.

The Gates Foundation found a Japanese encephalitis vaccine from China. The price is much lower than similar products, but it has not been pre-certified by the World Health Organization. Therefore, the Gates Foundation passed the PATH for this vaccine. By providing support, it helped it successfully pass the WHO pre-qualification in 2013, which is also the first vaccine product in China to pass the WHO pre-qualification. The Chinese JE vaccine, which is cheaper and more produced, helps more low-income countries to incorporate the JE vaccine into their national immunization programs. So far, more than 400 million children in 12 countries have been protected with the help of this vaccine.

Through various charitable organizations and the public and private social sectors, the problem of vaccine difficulties has been effectively helped in developing countries and poor areas. However, in the early stage of the epidemic, some routine immunizations suffered serious setbacks, although the situation appeared in late 2020. improved, but routine immunization needs to continue to be strengthened, and poor children in remote areas need special attention.

“We call these children ‘zero-dose children’, meaning they haven’t even had a single shot of those routine life-saving vaccines. Two-thirds of these children live below the poverty line. Only coverage These children, they are able to live healthy lives with many other socioeconomic benefits,” said Seth Berkeley. It is understood that Gavi’s work has reached over 900 million children and prevented over 15 million deaths.

It is understood that the Hib vaccine (Bacillus bleedere vaccine) has been available for more than 20 years. In a highly developed city such as Shanghai, the vaccination rate among school-age children in 2017 was 75.8%, but the economic burden is the most serious. In the five western provinces, the vaccination rate is less than 20%, and even only 3% to 7%. Such a technology is very mature and there is a very sufficient supply of vaccines, but regional differences are still very large.

Du Heng, senior project officer of the Gates Foundation, analyzed that if everyone is vaccinated, there must be a certain amount of financial investment and a certain degree of strategic support in the system. In Du Heng’s view, only the national immunization program can cover the most in need.

In Seth Berkeley’s view, to save more lives, we need to work with stakeholders to ensure that all children around the world have access to vaccinations and other basic health care facilities, while developing resilient worldwide Building health capacity to better meet future challenges.

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