Popular science: Why is the development of new crown virus vaccine so slow?

"We are flying while building an airplane." At a seminar on the new crown virus vaccine held recently, Gregory Pollen, director of the Mayo Clinic's vaccine research department and editor of "Vaccines" weekly, described the development of the new crown virus vaccine Urgency and high risk.
As the epidemic continues to spread globally, people are looking forward to more effective vaccines. However, no matter how urgent the need is, due to safety considerations, the development of new crown virus vaccines has to "have to be slow" and cannot cross the scientific process of vaccine design and production.
Vaccine development needs to be "targeted"
Since the early embryo of the vaccine, vaccinia vaccination, was born in the 18th century, the vaccine has become a solid "protective shield" for humans to fight the virus. Smallpox, measles, polio, hepatitis B and other infectious diseases that have raged around the world have been effectively controlled through vaccination.
However, vaccine research and development is a time-consuming, high-risk, high-investment task that requires preliminary design, animal experiments, and a total of three clinical trials. Depending on the type of virus and the technology used, it can take as short as three to five years and as long as ten years. World Health Organization Director-General Tan Desai said in February that the new crown virus vaccine is expected to be "ready" within 18 months. This is already quite fast.
To develop a vaccine, you must first understand enough about the virus to be "targeted." Although we do not yet have a comprehensive understanding of the new coronavirus, scientists are not completely "from scratch", and the research experience of other coronaviruses is the basis.
"New coronavirus is the third coronavirus that has spread to humans in large numbers through animal transmission in the past 18 years. With experience in dealing with severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), we have established relevant The technology platform has accumulated available data. This allows us to learn more about the new crown virus and obtain the virus sequence. Its receptor crystal structure has been resolved and identified as the "angiotensin converting enzyme 2 (ACE2)" receptor. We also have Candidate vaccines developed based on SARS. "Pollen said.
The study found that the new crown virus mainly infects the human body through the spike protein on the surface of the virus in combination with the human ACE2 receptor. Spike protein is like a "key", and ACE2 receptors on the cell are like a "lock". Only when the key is unlocked can the virus enter the cell. Therefore, the main goal of developing a new crown virus vaccine is to prevent the "key" from being opened to prevent the virus from infecting cells.
Based on the viral genome sequence provided by China, researchers at the University of Texas at Austin and the National Institutes of Health used cryo-electron microscopy to reconstruct the 3D conformation of the spike protein on the surface of the new coronavirus at the atomic scale. Researchers at Tsinghua University, West Lake University and other institutions also analyzed the crystal structure of the spike protein and ACE2 complex. These studies have provided the basis for identifying the main targets of vaccines and helped to find more precisely the mechanism that prevents "key unlocking".
New technology security needs to be tested
In addition to understanding the virus, improving vaccine preparation technology is also challenging. We can think of a vaccine as a virus or part of a virus that has been "transformed" by inactivation, attenuation, and other means. It can stimulate the body to produce an immune response, which in turn produces protective antibodies and immune memory against the virus, but does not make people infected with the virus. When the human body encounters a live virus again after being stimulated, the immune system that has already undergone the "exercise" can quickly respond and wipe out the virus.
Vaccine preparation technology has undergone multiple "evolutions". The most common vaccines are the first-generation live attenuated vaccines and inactivated vaccines, which are easy to make and have good immune effects, but the components are complex and there is a risk of recovery of virulence after vaccination; the second-generation vaccines include polysaccharide vaccines, subunit vaccines and peptide vaccine It has a single component and high safety, but its immune effect is relatively low. The third generation vaccine is a gene vaccine and a genetic engineering vector vaccine represented by DNA vaccine and messenger RNA (mRNA) vaccine.
Tan Desai said recently that more than 20 new crown virus vaccines are currently being developed worldwide. Live attenuated vaccines, subunit vaccines, and gene vaccines are the current technological pathways used by institutions to develop new crown virus vaccines.
The first batch of new crown virus vaccines for clinical trials produced by American biotechnology company Modena recently adopted the third-generation vaccine technology. This technology can use mRNA to induce the immune system to respond to proteins in pathogens, but at present no finished mRNA vaccine has been released in clinical trials around the world, and its safety and effectiveness need to be tested.
There are many risk factors that cannot be ignored in vaccine development. For example, experts are generally concerned about the "disease enhancement" problem, that is, the vaccine may make the vaccinated population more sensitive to the next infection or other viral infections. In addition, researchers also hope to introduce international standards for measuring vaccine effectiveness, such as the ability to find biomarkers in the blood that reflect antibody levels.
In addition, after the vaccine is developed, whether it can be produced on a large scale, the convenience of storage, and the convenience of transportation will also directly affect the "schedule" of people's final vaccination.
However, if the new crown virus becomes a seasonal epidemic, the development and promotion of vaccines will become the most important control measures.
"When we encounter these new viruses, especially coronaviruses, the long-term hope for prevention and control lies in vaccines. In other words, we need to prevent infections, not just rely on treatment." Pollen said, "Coronaviruses, especially ( "New coronavirus belongs to the beta coronavirus, which will not disappear soon."