Vaccines are a protective shield against viruses: smallpox, a virulent infectious disease that has plagued humans for thousands of years, was eradicated as a result of the spread of vaccines.Measles, polio, hepatitis b and other infectious diseases that once ravaged the world have been effectively controlled through vaccines.
In the context of the novel coronavirus pandemic, it is expected that the novel coronavirus vaccine will be developed as soon as possible to provide protection for humans.However, the development of covid-19 vaccine still faces many difficulties and obstacles.
The first difficulty is to know the new enemy
To defeat a new enemy, you must first know and understand it.Novel coronavirus is the third coronavirus in the past 18 years to cause large-scale human infections through cross-species transmission, following SARS and MERS.
Experience with viruses of the same species can help us better understand our new enemies.Unfortunately, no vaccine against a coronavirus has been developed, and neither SARS nor MERS has been successfully marketed.Compared with other viruses, we still know little about the biological characteristics of novel coronavirus, the process of infection, pathogenicity, and the immune response to it.It will take us a lot of time to understand novel coronavirus.
Although no coronavirus vaccine is available, SARS and MERS have raised our awareness of coronavirus.After the outbreak, Chinese scientists quickly completed novel coronavirus gene sequencing and strain isolation, laying a solid foundation for vaccine research and development.
Novel coronavirus mainly infects humans by binding the Spike protein on the surface of the virus to the human ACE2 receptor.The S protein ACTS like a key, and the ACE2 receptor ACTS like a lock. When the key is unlocked, the virus enters the cell.The main goal of developing a vaccine is to prevent the virus from infecting cells by preventing the key from opening the lock.The basic research of scientists can help people find the target of covid-19 vaccine and find ways to stop the key from opening the lock.
The second difficulty is that the enemy will change
Novel coronavirus is a highly glycosylated RNA virus, which means it can easily morph, rendering the vaccine ineffective.
Glycosylation is an extensive and complex post-translational modification of proteins, which plays an important role in cells and organisms.Some scholars have compared the glycosylation sites of common enveloped viruses: hepatitis c virus has 4-11 glycosylation sites, influenza virus has 5-11 glycosylation sites, ebola virus has 8-15 glycosylation sites, and HIV has up to 20-30 glycosylation sites.
These glycosylation sites predispose the virus to multiple mutations.When the virus is glycosylated, it is disguised as a “mask”. The antibodies produced by the vaccine may not be able to accurately identify the virus in the body, and thus cannot prevent it.The glycosylation site of HIV is three to six times higher than that of influenza, which is one of the main reasons why the development of an AIDS vaccine has been delayed.
According to the latest research, novel coronavirus is a highly glycosylated spherical particle with a huge structure and at least 66 glycosylated sites!Novel coronavirus has at least twice the glycosylation site of HIV, which means vaccine development is extremely difficult.
The third difficulty is to turn the weapon against yourself
The covid-19 vaccine is a weapon for humans to deal with the virus, but the increased antibody dependence (ADE) effect may make this weapon in turn deepen the harm to humans.ADE function refers to that, when the body encounters pathogen infection, the original neutralizing antibodies can not only prevent the virus from invading human cells, but also significantly enhance the replication or infection capacity of some viruses with the assistance of specific antibodies, leading to more serious pathological damage.ADE effect is one of the major obstacles in the development of dengue vaccine.For example, a dengue vaccine given to children in the Philippines in 2016 killed about 600 children.
The ADE effect was found in primate studies of SARS vaccine development: if monkeys were infected with the virus after inoculation with a recombinant vaccine-sars vaccine that expressed the virus’s spike protein, acute lung injury would be aggravated.Novel coronavirus vaccine also has the risk of ADE action due to its similar spike protein structure and infection mechanism between novel coronavirus and SARS virus, so it should be carefully studied in vaccine design.
There is, however, some good news on this front.On May 6, Chinese scientists first published the animal experiment results of novel coronavirus vaccine in the international top academic journal Science: rapid development of inactivated sars-cov-2 virus vaccine.The researchers developed a purified inactivated novel coronavirus vaccine candidate for use in animal experiments.In four rhesus monkeys in the high-dose group, no virus was detected in the throat, anus, and lungs, and no antibody dependence enhancement (ADE) was observed at 7 days after infection.
In addition to the three difficulties mentioned above, there may be many unexpected difficulties to be overcome in the development of covid-19 vaccine, because there is no guarantee that the vaccine development will be successful.HIV is an RNA virus that began developing a vaccine in the 1980s, but has so far been unsuccessful.Respiratory syncytial virus, which is also an RNA virus, is a typical respiratory virus, and has been studied for 50 years with no results.
However, the development of covid-19 vaccine in China is progressing smoothly, which gives people confidence in the results.Wang junzhi, academician of the Chinese academy of engineering, has made it clear that up to now, vaccines in China’s five major technical directions are generally progressing smoothly.The development of covid-19 vaccine in China is currently among the most advanced countries in the world and will not be slower than that in other countries.