Photo: The Beijing Advanced Innovation Center for Genomics at Peking University

As the world remains in almost a standstill and silenced after being ravaged by the novel coronavirus, scientists worldwide are sprinting to find solutions by researching vaccines and therapeutics. A Chinese research team spearheaded by Peking University (PKU) is taking the lead by unsheathing neutralizing antibodies, which will likely lay the foundation for potent COVID-19 treatment that would hopefully be available as early as this winter, in case of a resurgence of the virus.

The research team led by Sunney Xie, the director of the Beijing Advanced Innovation Center for Genomics at PKU, has successfully identified multiple highly potent neutralizing antibodies against the novel coronavirus SARS-CoV-2, the causative virus of the respiratory disease COVID-19, from convalescent plasma by high-throughput single-cell sequencing.

Such a drug would hopefully be able to stop the COVID-19 pandemic, in case the vaccine isn't available soon, Xie said in an exclusive interview with the Global Times on Wednesday. 

Milestone 

The team's research was published on last Sunday in Cell, a peer-reviewed scientific journal publishing research papers within the life sciences. Peking University hailed the achievement as a major scientific milestone in the fight against the pandemic. To make such phenomenal progress, it only took the team three months. 

Animal experiments on the neutralizing antibodies' efficacy turned out to be ideal, which also propelled the team to push forward clinic trials, added Xie, who is hopeful that an effective drug will come out this winter. 

Xie said he expects the antibodies to undergo clinical trials in July. "If the outbreak resurges this winter, hopefully our medicine is already available in the market."

After the COVID-19 outbreak, many research teams and scientists raced against time to develop a vaccine. However, because injecting a vaccine to healthy people requires extreme care, high technological threshold and long R&D cycle, Xie veered to another direction: an effective drug. 

Deploying high-throughput single-cell genome sequencing technology that Xie and his team skillfully specialize in, they found multiple highly potent neutralizing antibodies in the blood of recovered patients. "Our goal is to find high purity neutralized antibodies as soon as possible and inject them to patients, in place of plasma." 

"It was the first time this single cell genomic method was used to find human neutralizing antibodies," Xie said. 

Once offered tenure at Harvard University, but Xie gave up the position and returned to his motherland in 2018. After returning, Xie and his team focused on single-cell genome sequencing technology research, and tried to use this technology to improve the success rate of assisted reproductive treatment, which helped to prevent genetic disorders passing from parents to their newborns.

Identifying neutralizing antibodies in plasma was not an easy path for Xie and his team. It was like finding a needle in a haystack as there are hundreds of millions of types of antibodies. "But we have developed a methodology that allows rapid and successful screening of neutralizing antibodies," Xie said, predicting that single-cell sequencing technology will play an important role in drug development, accelerating the process and improving the efficiency.

Photo: The Beijing Advanced Innovation Center for Genomics at Peking University

For two months, Xie and his team had been working round the clock, and finally came up with an effective screening method. 

Xie said they worked on the efficiency by using magnetic beads to code with the viral protein and used them to pull out the B cells. And that allowed them to increase the efficiency to 20 percent. 

In addition, they obtained the crystal structure of a neutralizing antibody bond on the virus, which allowed them to gain molecular insight on how the neutralizing antibodies prevent the infection. Finally, they increased the efficiency of screening to 90 percent by using the predicted structures based on the sequencing results.

These potent neutralizing antibodies were isolated from the plasma samples of 60 recovered patients provided by the Beijing You'an Hospital, Capital Medical University, Xie said. 

He said they have successfully identified 14 neutralized antibodies with high activity. The antibodies are equipped with high activity, which gives it the power to contain the virus. A small dose can achieve the desired effect, Xie said, highlighting the low cost and high safety.  

According to Xie, five days after the team injected the BD-368-2 antibody in infected mice, the viral load in the animals' lungs declined by about 2,400 times. The antibody also proved effective in protecting healthy mice from the virus.

The animal tests were conducted by a team led by Qin Chuan, the director of the Institute of Laboratory Animal Sciences of the Chinese Academy of Medical Sciences and Peking Union Medical College, on a transgenic mice model they developed. 

Photo: Sunney Xie, director of the Beijing Advanced Innovation Center for Genomics at PKU

'Virus without borders'

Xie's team is working with WuXi Biologics, a Hong Kong-listed company, on clinical trials for the drug, which are expected to start in July in some foreign countries such as Australia. Not too many patients are available for testing in China, according to news portal yicai.com.

"Like any research, the process had not been plain sailing. There were ups and downs," Xie said, recalling the tough process of their research.

During the 2003 SARS crisis, it took about five months for scientists to sequence the virus, which was released by Canadian scientists. In the current COVID-19 pandemic, Chinese scientists completed the work in only a month.

Xie is regarded as a pioneer in single-molecule biophysical chemistry, Coherent Raman scattering microscopy, and single-cell genomics, and made major contributions to the emergence of these fields. 

Furthermore, he has made significant advances on medical applications of label-free optical imaging and single-cell genomics. 

One of his most significant achievements during his time at Harvard was the development of the MALBAC method to halt genetic diseases in embryos stemming from his collaboration with colleagues in China. His partners included Qiao Jie and Tang Fuchou, both professors at Peking University. Thanks to this technology, more than 1,000 babies were born free from the genetic disorders that their parents carried in China.

Xie said in a commentary titled "Diseases Have No Borders, Neither Should Research" published in the journal Cell in September 2019, that science should transcend politics and global scientists must collaborate. "My personal experience is an example of how US-China collaboration benefits the whole world, not just China."

The drug, if it succeeds, will be promoted globally, Xie said, noting that drug development -and scientific research in general - is always international. 

"The virus has no borders, neither does research, nor does humanity. Humanity is above all. If proven to be successful we want the drug to serve the world," Xie said.