Popular Science: Why is the development of the new coronavirus vaccine so "slow"

Source: Xinhuanet

"We are flying while making airplanes." At a seminar on the new coronavirus vaccine held recently, Gregory Pollen, director of the vaccine research department of the Mayo Clinic and editor-in-chief of the "Vaccine" weekly magazine, described the development of the new coronavirus vaccine. Urgency and high risk.

As the epidemic continues to spread worldwide, people are even more eager for effective vaccines. However, no matter how urgent the demand is, for safety reasons, the development of the new coronavirus vaccine is still "had to be slow" and cannot cross the scientific process of vaccine design and production.

Vaccine research and development should be "targeted"

Since the early prototype of the vaccine "vaccinia vaccination" was born in the 18th century, the vaccine has become a solid "protection shield" for humans to fight against viruses. Smallpox, measles, poliomyelitis, hepatitis B and other infectious diseases that have ravaged 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 phases of clinical trials. Depending on the type of virus and the technology path adopted, it generally takes as short as three to five years, and as long as more than ten years to go public. World Health Organization Director General Tan Desai said in February that the new coronavirus vaccine is expected to be "ready" within 18 months. This is already quite fast.

To develop a vaccine, you must first understand the virus enough to be "targeted." Although we still lack a comprehensive understanding of the new coronavirus, scientists are not completely "starting from scratch." Research experience with other coronaviruses is the basis.

"New coronavirus is the third coronavirus that has spread through animals to cause large-scale human infections in the past 18 years. With experience in dealing with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), we have established The technology platform has accumulated available data. This allows us to understand the new corona virus faster, get the virus sequence, its receptor crystal structure has been resolved and determined as the "angiotensin converting enzyme 2 (ACE2)" receptor, we also have Candidate vaccine developed on the basis of SARS. "Polun said.

The study found that the new coronavirus mainly infects the human body through the binding of the spike protein on the surface of the virus to the human ACE2 receptor. The spike protein is like a "key", and the ACE2 receptor on the cell is like a "lock." Only when the key is unlocked can the virus enter the cell. Therefore, the main goal of developing a new coronavirus vaccine is to prevent the "key" from opening the "lock" to prevent the virus from infecting cells.

Based on the viral genome sequences 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 from Tsinghua University, West Lake University and other institutions also analyzed the crystal structure of the spike protein and ACE2 complex. These studies have provided a basis for determining the main targets of the vaccine, and helped to find more accurate mechanisms that hinder "key unlocking".

New technology security to be tested

In addition to the need to strengthen the understanding of the virus, improving vaccine preparation technology is also quite challenging. We can think of a vaccine as a virus or virus component that has been "reformed" by means of inactivation, attenuation, etc. It can stimulate the body to produce an immune response, and then produce protective antibodies against the virus and immune memory, but it will 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 passed the "exercise" can quickly respond and wipe out the virus.

Vaccine preparation technology has experienced multiple generations of "evolution". The most common vaccines are the first-generation live attenuated vaccines and inactivated vaccines, which are easy to make and have good immunization effects, but the ingredients are complex and the risk of virulence recovery after vaccination; the second-generation vaccines include polysaccharide vaccines, subunit vaccines and peptide vaccine , Single ingredient, high safety, but relatively low immune effect; the third generation vaccine is a genetic vaccine and genetic engineering carrier vaccine represented by deoxyribonucleic acid (DNA) vaccine and messenger ribonucleic acid (mRNA) vaccine.

Tan Desai said recently that more than 20 new coronavirus vaccines are currently being developed worldwide. Live attenuated vaccines, subunit vaccines and genetic vaccines are the current technology paths adopted by various institutions to develop new coronavirus vaccines.

The first batch of new coronavirus vaccines for clinical trials produced by the US 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 there is currently no finished mRNA vaccine that has completed clinical trials in the world, and its safety and effectiveness are yet to be tested.

There are many risk factors that cannot be ignored in vaccine research and development. For example, experts generally pay attention to the "enhanced disease" problem, that is, the vaccine may make the vaccinated people more sensitive to the next infection or other viral infections. In addition, the researchers also hope to introduce international standards for measuring the effectiveness of vaccines, such as whether biomarkers reflecting antibody levels can be found in the blood.

In addition, after the vaccine is developed, various factors such as the scale of production, storage, and convenience of transportation also directly affect the "timetable" for people to be vaccinated.

But if the new coronavirus becomes a seasonal epidemic disease, the development and promotion of vaccines will become the most important control measures.

"When we encounter these new viruses, especially coronaviruses, the long-term prevention and control hope lies in vaccines. In other words, to prevent infections, not just rely on treatment." Pollen said, "Coronaviruses, especially ( The new coronavirus belongs to) β is a coronavirus and will not disappear soon. "