(Fighting against New Coronary Pneumonia) Xie Xiaoliang, Academician of the Fourth Academy: Looking for New Coronavirus Neutralizing Antibodies
China News Service, Beijing, April 5 Question: Xie Xiaoliang, "Academician of the Fourth Academy": Looking for New Coronavirus Neutralizing Antibodies
China News Service reporter Zhang Su
"We screened the 300 most enriched IgG antibody sequences from the 300,000 B cells in the plasma of 70 convalescent patients. We are currently testing 300 antibody proteins produced based on these sequences. A large number have been screened Antibodies with high binding strength and multiple antibodies with excellent neutralizing activity, "said Xie Xiaoliang, director of the Center for Biomedical Innovation at Peking University.
As a member of the "Four Academicians" (member of the National Academy of Sciences, member of the National Academy of Medicine, member of the American Academy of Arts and Sciences, foreign member of the Chinese Academy of Sciences), Xie Xiaoliang was recently invited by the Future Forum to introduce the team in the "Understanding the Future" scientific lecture Research progress.
After the outbreak of New Coronary Pneumonia, Xie Xiaoliang and colleagues began looking for neutralizing antibodies against New Coronavirus from the third day of the first lunar month. "As scientists in the rear, at the beginning we just wanted to do something for the anti-epidemic. When we realized that single-cell genomics might have the potential to help find neutralizing antibodies, we were very excited." He recalled.
It is well known that acid-base neutralization, and the role of neutralizing antibodies is to firmly bind the virus and change its function when the virus invades the human body. Including Xie Xiaoliang's team, many Chinese and foreign scientific research teams are seeking to quickly find and prepare high-purity neutralizing antibodies and use them as drugs to replace plasma. Recently, the team of Zhang Linqi, a professor at the School of Medicine of Tsinghua University, announced the results of the new coronavirus neutralizing antibody experiment and stated that "neutralizing antibodies may become an effective substitute."
Why do we seek to "neutralize" in the face of the new crown virus? Xie Xiaoliang explained that on the one hand, small-molecule drugs such as chloroquine and hydroxychloroquine are only new drugs used in old medicines with limited efficacy. Although plasma therapy works, it also has certain risks and cannot be used on a large scale. On the other hand, neutralizing antibody drugs have been used to "block" HIV, Ebola virus, MERS (Middle East Respiratory Syndrome) virus and other invasions. In recent years, single-cell genomic technology has developed, including single-cell amplification technologies such as MALBAC and LIANTI, which were invented by his Harvard laboratory, have greatly improved the throughput and accuracy of single-cell analysis, making it possible to quickly find neutralizing antibodies. .
But this work is still full of challenges. For example, the number of antibodies in the plasma is about 10 to the 7th to 8th power. If you want to directly find the new coronavirus neutralizing antibody, it is like a needle in a haystack. Another example is that the number of IgM antibodies and IgG antibodies changes with time, of which IgG antibodies are infected in humans. The new coronavirus will only appear after one or two weeks and will decrease after three or four weeks, so there is a time limit for the return visit of discharged patients; for another example, in the past, the single-cell cloning amplification method used to take up to several months, and now they must The virus "runs".
Over the past two months, Xie Xiaoliang's team has cooperated with Beijing Youan Hospital affiliated to Capital Medical University and has made progress in succession. They used single-cell transcriptome experiments to type thousands of immune cell B cells in the blood of convalescent patients, focusing on memory B cells; they used a "magnet" to separate from the blood to bind S protein or RBD (receptor binding) Domain) bound memory B cells, greatly improving the screening efficiency; they measured the binding strength of the antibody, and found that the strength of the binding of the selected antibody to the viral S protein is much higher than ACE2 (angiotensin converting enzyme 2), and the new crown is recognized by the academic community The virus uses the ACE2 to turn on the human protection "switch"; the data of the new corona virus neutralization test in human Vero E6 cells also shows that the neutralizing antibody can effectively inhibit the virus infection at a low concentration (1μg / mL).
"We can quickly and accurately screen out a large number of high-quality neutralizing antibodies." Xie Xiaoliang revealed that follow-up animal experiments are being planned, and clinical trials will be conducted later. These neutralizing antibodies have at least three applications. First, it can be used for the treatment of neutralizing antibody against new coronary pneumonia, "safer and more targeted". Second, it can be used for short-term prevention. "The validity period is about three weeks, and it may be extended to three months after transformation." Thirdly, this method has made technical preparations for future outbreaks.
However, scientists including Li Wenhui, a senior researcher at the Institute of Beijing Institute of Biological Sciences, pointed out that compared with small molecule drugs, macromolecular drugs such as neutralizing antibodies have the advantages of less administration and high safety, but they also face challenges In particular, there may be an antibody-dependent viral infection enhancement effect (ADE).
Xie Xiaoliang explained that neutralizing antibodies do sometimes have side effects of ADE-antibodies bind to the virus and then pull the virus into human cells, which of course must be avoided. "The good news is that ADE is still relatively rare." He said, and this problem can be solved by screening neutralizing antibodies that do not produce the ADE phenomenon. Another piece of good news is that although it is still difficult to determine whether the epidemic will be repeated this year, he is optimistic: "If the virus comes back in October, then our neutralizing antibody may have been successfully developed."
"Viruses have no borders, so should the anti-epidemic." As a scholar who has worked in the top universities in China and the United States for many years, Xie Xiaoliang emphasized in particular. "If (neutralizing antibody) is made into medicine, we will not name it" Chinese antibody "because its use should have no borders." He said, and called on young people to love science and devote themselves to science. This epidemic confirms the importance of science. "We firmly believe that science can overcome viruses and save humanity from disaster." (Finish)