On May 22, the lancet, a prestigious medical journal, published online the clinical data of human trials of the covid-19 vaccine by the team of academician Chen wei from the Chinese academy of military medicine and professor zhu fengcai from the jiangsu provincial center for disease control and prevention.
The results showed that the vaccine could induce a rapid immune response.
This is also the world’s first human clinical data of covid-19 vaccine.
What does this breakthrough mean for resistance against novel coronavirus?
Does this mean a covid-19 vaccine is not far off?
Interviewed expert: Yang zhanqiu, professor of the institute of virology, school of medicine, wuhan university
This article author | life times reporter gao Yang this article editor | xu wenting
Unprecedented advances in research
Since her arrival in wuhan on January 26, academician Chen wei has led a research team to focus on the research and development of vaccines. The researchers used the novel coronavirus vaccine based on recombinant adenovirus type 5 (Ad5) as the carrier.
Academician Chen wei’s team is on the front line of the battle against the epidemic in wuhan
The Ad5 is an engineered common cold virus (which infects human cells but cannot replicate or cause disease) that transmits genetic material encoding a novel coronavirus spike protein to cells that produce a spike protein that travels to lymph nodes, where it generates antibodies to fight against novel coronavirus.
On March 16, the vaccine was registered for clinical trials and entered clinical trials.
A total of 108 volunteers were vaccinated in the first phase.
At 20:18 on March 16, the vaccine was officially approved for clinical trial
The results showed that the volunteers all showed immunogenicity and human tolerance.
The humoral immune response of healthy adults to novel coronavirus peaked 28 days after vaccination.
The specific T cell response peaked 14 days after inoculation.
Specific T cell responses were measured by elisa (ELISpot)
At present, phase ii clinical trial has been launched, and 508 volunteers have been injected and are under observation. If everything goes well, the blindness will be revealed in May.
This vaccine is the first covid-19 vaccine approved for clinical study in China, and also the first covid-19 vaccine to enter phase ii clinical trial in the world, and has been recognized by the world health organization.
“These results are an important milestone,” Chen said.
Tests showed that the vaccine could induce a virus-specific antibody and t-cell response within 14 days, making it a potential candidate for further research.
Richard horton, chief editor of the lancet, said the vaccine developed in China was safe and well tolerated, and could induce a rapid immune response.
“The development is unprecedented,” the dpa said.
“This is an exciting result!”
Yang zhanqiu, a professor at the institute of virology at the basic medical college of wuhan university, said that the clinical results showed that the vaccine design was “successful” in getting all the volunteers to respond to the virus.
Professor wang, an immunology expert who was once involved in the research of SARS vaccine, also expressed his affirmation: “in the phase I clinical trials, there is not only the response of antibodies, but also the response of T cells, which proves that its immunogenicity is very good.”
Yang zhanqiu explained that immunogenicity is a very important indicator to evaluate the early efficacy of vaccines. Without immunogenicity, the protective effect of vaccines would be impossible to talk about, and the vaccine showed good safety after vaccination. All these provide a feasible scientific basis for the next clinical trials.
Clinical applications are still a long way off
Because of the outstanding clinical results in phase I, the outside world has speculated that the new coronavirus vaccine is not far from the market.
However, Chen said, “these results should be interpreted with caution. The challenges facing the development of a covid-19 vaccine are unprecedented, and the ability to trigger these immune responses does not necessarily mean that the vaccine will protect humans from covid-19.”
“This result only shows the hope for the development of a covid-19 vaccine, which is still a long way from being available to all.”
The report said the trial had small sample sizes, a short trial period, a lack of randomised controls, and the volunteers were all under 60, with only 16% over 50, so further trials are needed.
Yang believes that the next step of clinical trials should be to expand the population, inoculate susceptible groups such as the elderly and doctors in different regions and ethnic groups, and observe the immune effect at different doses.
The presence of antibodies does not necessarily mean the absence of infection
The Oxford coronavirus vaccine, which had been said to be ready for use as soon as September this year, was given to six monkeys and all developed antibodies, but the development was recently declared a failure because the infected monkeys became infected with the novel coronavirus and showed the same symptoms as the unvaccinated monkeys.
Wang explained that the production of antibodies is the basis of the vaccine, but whether there must be protection, or whether the chance of protection reaches 100 percent, remains to be confirmed by further studies.
Also, the amount and type of antibodies produced is important.
For example, hepatitis b has a protective effect only if it produces surface antibodies, which are useless if it produces e-antigen antibodies.
The safety and comfort of vaccines need to be improved
Age, according to data from the team’s research within 7 days after inoculation, 87 people (81%) reported at least one adverse reactions, more than half reported pain at the injection site, the most common systemic adverse reactions are fever, fatigue, headache and muscle pain, most adverse reactions are mild or moderate, with no serious adverse event reports within 28 days.
Yang zhanqiu believes that this kind of adverse reaction rate is relatively high.
Although fever after vaccination is normal, it also suggests that the purity of the vaccine may not be high enough, and that the manufacturing process needs to be improved to reduce the rate of fever and pain.
If most people experience discomfort after vaccination, even if it is temporary, it may be unacceptable to many.
R&d faces many variables
To evaluate whether the vaccine is effective, Yang says, do a challenge test, exposing healthy people who have been vaccinated to pathogens to see if they can become infected.
However, from an ethical point of view, it is not possible to expose healthy people to the virus completely, so it is necessary to take the vaccinator’s serum and neutralize it with live virus in the laboratory to see if it is infected, thus indirectly proving the effectiveness of the vaccine.
Even if phase I and ii trials go well, phase iii is fraught with uncertainty.
Because phase iii requires tens of thousands of subjects, the trial can only be carried out smoothly if it is still in the epidemic period. This is one of the important reasons why the clinical trial of the SARS vaccine, which entered into phase I human trials in 2003, has not been completed.
In addition, if the novel coronavirus mutated, the original vaccine would still be effective and safe.
A successful vaccine is not the end of the epidemic
Currently, there are more than 5 million confirmed cases of covid-19 worldwide, and more than 300,000 people have died from the disease.
An effective vaccine is seen as a long-term solution to contain the covid-19 pandemic, and the world is racing against time to develop it.
According to the statistics of the world health organization, there are more than 120 vaccine development projects in the world. As of May 22, 10 covid-19 vaccines have been in clinical trials (5 of them from China) and 114 of them have been in preclinical studies.
Among them, the fastest progress is the novel coronavirus vaccine developed by the team of academician Chen wei. The latest experimental results were released and a dose of “cardiac booster” was injected into the global covid-19 epidemic prevention and control.
In addition, a number of companies and scientists have carried out research and development from five technical routes: inactivated vaccine, recombinant protein vaccine, adenovirus vector vaccine, attenuated influenza virus vector vaccine and nucleic acid vaccine.
The future of covid-19 vaccines could involve the vaccination of billions of healthy people, and its safety is key.
Professor Yang zhanqiu and professor wang agreed that the most optimistic about the inactivated vaccine.
Yang zhanqiu explained that the inactivated vaccine is a traditional classic vaccine, although the technology is conservative, but the process is mature, the safety and effectiveness is better, people have more research experience on it.
Professor wang also said that the safety of the inactivated vaccine “in the bottom of the mind.”
As for other vaccines, there are many studies on recombinant protein vaccines, such as hepatitis b vaccine and HPV vaccine.
At present, adenovirus vector vaccine has not been used on a large scale in the world, and its safety is not clear.
Genetically engineered vaccines use only one gene from the virus, and if the virus mutates, it may not work as well.
Based on past experience, professor wang is cautiously optimistic that a covid-19 vaccine can be developed successfully.
He said that since the discovery of the coronavirus in the 1960s, no vaccine has been developed and there is no reliable previous experience to draw on.
Many new technologies have been used to overcome previous failures, but it is unclear whether they will be successful.
For example, in the development of covid-19 vaccine, scientists are very optimistic about an antigen — S protein, but its glycosylation level is particularly high, which will affect the immunogenicity and antigenicity, causing some difficulties in the development of vaccine.
Professor wang stressed that vaccine research should not be rushed and should be down to earth.
The 1976 swine flu vaccine in the United States was a failure. It took months to roll out, calling for mass vaccination, and hundreds of people developed guillain-barre syndrome and even died.
Even if the vaccine is developed successfully, the vaccine effect is good or bad. For example, the protection effect of cholera vaccine and plague vaccine is not ideal, which can only protect part of the population, and the immune protection period is short.
Therefore, the covid-19 epidemic cannot be controlled by the vaccine alone.
Yang said the success of the vaccine only provides a powerful means to control the epidemic, and does not mean the epidemic is over.
Even if a vaccine is developed, the outbreak could return in the winter if it is not controlled properly.
Experts expect at least three to six months of phase iii clinical trials, with results by the end of this year or early next year at the soonest. The vaccine could be tested in a state of emergency, but mass vaccination is still a long way off.