China’s Vaccine Front-Runner Aims to Beat Covid the Old-Fashioned Way

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Many of the200-plus Covid-19 vaccine projects under way around the world are focused on new technologies—inoculations based on messenger RNA, for example, or genetically modified cold viruses. The company developing one of China’s leading vaccine candidates, by contrast, is betting that humanity’s best chance may lie with a shot not too different from the kind that’s been in use for hundreds of years.

Beijing-basedSinovac Biotech Ltd., a company with a strong medical track record but a turbulent corporate history, began final-stage trials in July on CoronaVac. It relies on an inactive version of the novel coronavirus to teach human immune systems to recognize and destroy the real thing. In terms of timing, the company was ahead of most other potential vaccines, including the new models meant to facilitate strong protection and fast production. Sinovac’s candidate has a good chance of entering commercial production almost as quickly asModerna Inc.’smRNA vaccine, or thegenetically modified shot being developed by theUniversity of Oxford andAstraZeneca Plc.

Sinovac’s method is relatively crude, relying on a similar principle to the one Edward Jenner, the 18th century British scientist sometimes called the father of immunology, employed when he used the mild cowpox virus to perform the first-ever inoculations against smallpox. But it just might work—and it could be easier to use than the never-before-tried approaches of other companies.

“We’ve got to learn about history and not forget what’s worked in the past,” says Michael Kinch, a vaccine specialist at Washington University in St. Louis. “Don’t get fancy when simple will do it for you just as well.”

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There’s a case to be made that traditional vaccines could be most effective in stopping Covid-19, which haskilled about 800,000 people worldwide. Many of the new vaccine approaches focus on replicating the distinctive“spike” protein on the surface of the coronavirus, which helps it invade human cells. Data suggest that if the immune system can block that protein, the virus’s attack will be significantly blunted, if not stopped. But it could be preferable to expose the body to most or all of the virus, giving it a far broader choice of potential targets and letting the immune system decide which are the most vulnerable.

The advantage of a whole-virus approach is that “you are putting in many kinds of proteins,” says William Haseltine, a pioneering AIDS researcher who now chairs Access Health International Inc., a New York-based think tank. “Many of those proteins may induce cell-mediated immunity”—an attack by so-called T cells, for example, rather than just antibodies. It’s far from certain, he says, “but it is clearly a possibility.”

Other benefits might emerge when it comes time to produce and distribute the shot. While no mRNA vaccine, for example, has ever been licensed for human use, manufacturers have decades of experience with inactivated-virus inoculations, making production problems unlikely. And those vaccines generally don’t need to be frozen, a significant boon in developing countries and rural areas where refrigeration capacity may be limited. (CoronaVac, for example, can be stored at between 36F and 46F.)

On the other hand, inactivated vaccines can require several booster shots to achieve strong immunity, and production means handling large amounts of a dangerous virus. In theory, mRNA vaccines should also be much faster to manufacture, because they require only tiny volumes of raw material to produce millions of doses.

Winning approval for CoronaVac would be a huge coup for Sinovac—and for Chinese President Xi Jinping’s effort to put the country at the forefront of rolling out a vaccine. The company is led by Yin Weidong, who began his career in the early 1980s at a public-health unit in the northeastern city of Tangshan. On his first day of work he was assigned to a group investigating hepatitis outbreaks in the surrounding countryside. He went on to spend much of his career focusing on how to prevent and control the debilitating liver disease in rural China. He founded Sinovac in 2001, not long before an earlier coronavirus—the one that caused severe acute respiratory syndrome, or SARS—roiled the country. Sinovac developed a potential SARS vaccine, but the disease faded away before it could be put into use. The company later won approval for a shot targeting H1N1, or swine flu.

As coronavirus infections surged in China early this year, Sinovac began evaluating its options for developing a new vaccine, Yin says. Everything was on the table, including a high-tech, genetically engineered approach. Company executives decided that a tried-and-true method stood the best chance of success in a fast-moving pandemic. “We had the technology ready,” Yin says. “Back in 2003, when we were developing vaccines for SARS, we learned a lot about the biology of coronavirus, how to inactivate it and grow it in batches.”

To produce its inactivated virus, Sinovac obtained samples of the Covid-19 pathogen from patients around the world and let them multiply in vero cells, which are derived from the kidneys of monkeys. It then rendered the virus inactive using beta-propiolactone, a chemical derived from formaldehyde that’s often employed in vaccine research, before purifying it into a product suitable for injection—first in mice, rats, and primates, and then in humans in early studies.

The company is waiting for data from its final-stage trials, including astudy of about 9,000 people in Brazil, that will determine whether the vaccine is safe and can prevent disease on a large scale. If the trials are successful, Sinovac plans to produce at least 300 million doses a year in its own factories while tapping other manufacturers for further production.

Investors looking to get a piece of Sinovac’s potential success will, however, be disappointed. Its shares, which are listed on Nasdaq, have been suspended from trading for more than a year, the result of a complex and unresolved dispute with some of its own investors. The drama began in 2016, when two groups of shareholders—one led by Yin and another by Pan Aihua, Yin’s former mentor and the chairman of one of Sinovac’s largest shareholders—made competing offers to take the company private.

The board eventually approved Yin’s offer, spurning a higher bid from Pan. Two years later, in 2018, a group of investors sought to remove Yin and several other executives from the board. In response, Sinovac moved to massively dilute its shares to reduce the power of Yin’s critics, triggering the trading halt.

The shareholder dispute remains before the courts, and in June Sinovac said it couldn’t estimate when it will be able to resume trading. That means it’s recorded nothing like the soaring gains of Moderna, whose shares have tripled in value since the beginning of the year amid optimism about its Covid-19 vaccine. Moderna is now worth about $27 billion—60 times Sinovac’s valuation of roughly $460 million, which has been frozen since February of last year.

All that is hardly a concern for China’s government, as it’s identified rapid vaccine development as a key plank in its post-pandemic geopolitical strategy—and an opportunity to show that its biotech companies can compete with the best. Beijing regulators are fast-tracking approvals and allowing experimental immunizations to enter human trials at an unprecedented pace—for example, by letting developers submit data as it’s collected rather than at the end of a research phase. Without those measures, Yin says, Sinovac could never have entered the last stage of tests so rapidly. Xi has also promised toshare any successful vaccine globally, which could build goodwill with poorer countries fearful of being locked out by projects such asOperation Warp Speed, the Trump administration’s vaccine program.

Several other Chinese companies are well into human trials, including Tianjin-basedCanSino Biologics Inc., which has developed a vaccine that uses a harmless adenovirus to mimic the coronavirus’s spike protein—a similar approach to the Oxford group’s. A medical research institute affiliated with the Chinese military, meanwhile, is running a trial for an mRNA vaccine, comparable to the one created by Moderna. Another front-runner, state-controlled China National Biotec Group, is using an inactivated-virus approach along the same lines as Sinovac’s.

Even if the Chinese companies succeed in getting their vaccines approved, they’ll face a formidable challenge: convincing people that their products are safe, especially after a drastically accelerated approval process. Ironically, that may be toughest in their home market, where many consumers prefer Western pharmaceuticals. China’s vaccine industry has seen repeated scandals over the past decade. A Beijing court ruled in 2017 that an official at the country’s drug regulator received improper payments from vaccine producers including Sinovac. The U.S. Department of Justice and the Securities and Exchange Commission conducted related investigations of the company. Sinovac was never charged in either country.

A wider outcry occurred over subpar vaccines from some Chinese companies that may have failed to protect infants from such diseases as diphtheria and whooping cough. Last year, Beijing introduced a law to police the business, imposing far stricter rules on development and threatening heavy fines or jail time for violations.

Sinovac is eager to demonstrate that it can meet the same standards as U.S. or European competitors. Itpublished the results of its animal trials in the journal Science in May, reporting that its coronavirus vaccine had produced effective antibodies across multiple species. Data from its early human trials, which the company said showed the injection was safe and produced an immune response, have so far been provided only in a press release, not a peer-reviewed journal, but Yin says the company intends to make all of its results available. “We can present every test, every product, and every result to global scrutiny,” he says. “And we can compare with other products, so it will be clear whose is good and whose is not.”

If Sinovac’s last phase of trials is successful, CoronaVac could be deployed at large scale next year. For health experts, anygeopolitical consequences of the company finishing at or near the front of the pack are far less important than the medical benefits of having more options to protect against the coronavirus. “If we have one vaccine that works, the world has failed,” says Mike Turner, head of major science investments atWellcome, a London-based medical foundation. “We need to have several different vaccines. It’s not that we will have one miracle silver bullet.” —James Paton, Dong Lyu, and John Lauerman
 
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