Why is the development of the new coronavirus vaccine so “slow”? Lack of a comprehensive understanding of the virus, security to be tested

“We are building planes while flying. Gregory Boren, director of vaccine research at the Mayo Clinic in the United States and editor-in-chief of Vaccine Weekly, described the urgency and high risk of developing a new coronavirus vaccine at a recent symposium on the vaccine.

As the outbreak continues to spread around the world, there is renewed hope for an effective vaccine. However urgent, the development of the new coronavirus vaccine has “had to be slow” for safety reasons, not across the scientific process of vaccine design and production.

Vaccine development needs to be “targeted”

Since the early days of the vaccine “cowpox vaccination” was born in the 18th century, the vaccine has become a solid “protection shield” in the human struggle against the virus. Smallpox, measles, polio, hepatitis B and other infectious diseases that have ravaged the world, have been effectively controlled through vaccination.

However, vaccine development is a time-consuming, high-risk, high-cost task that requires pre-design, animal trials, and a total of three clinical trials. Depending on the type of virus and the use of technology path, the general short three to five years, the length of ten years before the listing. World Health Organization Director-General David Tan de Sai said in February that the new coronavirus vaccine was expected to be “ready” within 18 months. That’s pretty fast.

The development of a vaccine must first have a sufficient understanding of the virus itself in order to be “targeted”. Although we still lack a comprehensive understanding of the new coronavirus, scientists are not completely “starting from scratch”, and the research experience of other coronaviruses is the basis.

“The new coronavirus is the third coronavirus in the past 18 years to spread through animals and cause large-scale human infection. With experience in dealing with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), we have established a technical platform that has accumulated available data. This gives us a faster understanding of the new coronavirus, gets a sequence of viruses, its receptor crystal structure has been parsed and determined to be the “angiotensin conversion enzyme 2 (ACE2)” receptor, and we also have a candidate vaccine based on SARS. Bolen said.

The study found that the new coronavirus mainly infects the human body by binding the protrusion protein on the surface of the virus with the body’s ACE2 receptor. The protrusion protein is like a “key”, while the ACE2 receptor on the cell is like a “lock”. Only when the key is unlocked can the virus enter the cell. So 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.

Researchers at the University of Texas at Austin and the National Institutes of Health used a frozen electron microscope to reconstruct the 3D formation of protoproteins on the surface of the new coronavirus on an atomic scale, according to a virus genome sequence provided by China. Researchers at Tsinghua University, West Lake University and other institutions have also analyzed the crystal structure of the protrusion protein and ACE2 complex. These studies provide the basis for identifying the main targets for vaccines and help to find more precise mechanisms that block the “key lock”.

The safety of new technology to be tested

In addition to the need to strengthen understanding of the virus, improving vaccine preparation techniques is also challenging. We can think of vaccines as a virus or virus component that has been “modified” by means of inactivation and detoxification. It stimulates the body to produce an immune response, which in turn produces protective antibodies against the virus and immune memory, etc., but does not infect people with the virus. When the human body receives stimulation and then encounters live virus again, the immune system, which has already gone through “exercises”, can react quickly to the whole virus.

Vaccine preparation technology has undergone multiple generations of “evolution”. The most common vaccines are the first generation of detoxifying live vaccines and inactivated vaccines, easy to produce, good immune effect, but complex composition, toxic recovery risk after vaccination; The third generation of vaccines are gene vaccines and genetically engineered vector vaccines, represented by DNA (DNA) vaccines and messenger RNA (mRNA) vaccines.

Tandesser said recently, there are more than 20 new coronavirus vaccine steaming around the world. Detox-reducing live vaccines, subunit vaccines and gene vaccines are the more technical pathways used by agencies to develop new coronavirus vaccines.

The first new coronavirus vaccine for clinical trials by US biotech company Modena has adopted third-generation vaccine technology. The technique can use mRNA to induce the immune system to respond to proteins in pathogens, but the world has not yet completed clinical trials of the finished mRNA vaccine, the safety and efficacy of the test.

Vaccine development has many risk factors that cannot be ignored, such as experts’ widespread concern about “disease enhancement”, in which vaccines may make people more sensitive to the next or other infections. In addition, the researchers hope to introduce international standards to measure the effectiveness of vaccines, such as the ability to find biomarkers in the blood that reflect antibody levels.

In addition, after the development of the vaccine, whether the large-scale production, preservation and transportation convenience of many factors, but also directly affect people’s final vaccination “schedule.”

But if the new coronavirus becomes a seasonal epidemic, vaccine development and promotion will become the most important prevention and treatment measures.

“When we come across these new viruses, especially coronaviruses, the long-term hope of prevention and control lies in vaccines. In other words, prevent infection, not just rely on treatment. “Coronaviruses, especially beta-coronaviruses (to which the new coronavirus belongs), don’t go away any time soon, ” Boren said. “