With global push for COVID-19 vaccines, China aims to win friends and cut deals .

Covid-19 News

719 Views

        

Beijing-based Sinovac, which makes a COVID-19 vaccine from inactivated virus, has efficacy trials underway in Brazil, Turkey, and Indonesia—but not in China.

REUTERS/Thomas Peter

The first people in the world to receive a COVID-19 vaccine were not part of a clinical trial. No TV stations or newspapers covered the historic event. No company issued a statement.

On 29 February, less than 2 months after the world awakened to the threat of the new disease, virologist Chen Wei, a major general in China’s army, and six military scientists on her team stood in front of a Chinese Communist Party flag and received injections of an experimental COVID-19 vaccine. Chen, a national hero for her work on Ebola vaccines, had come to the initial center of the pandemic, Wuhan, with her group from the Academy of Medical Military Sciences, in part to help make the candidate vaccine with a commercial company, CanSino Biologics. Commentators inside and outside of China later questioned whether the event, which received wide play on social media, was real. No less than People’s Daily, the Communist Party’s main newspaper, labeled a photo of Chen receiving the vaccine as “#FAKENEWS.” But Hou Li-Hua, a researcher at the academy who works on the vaccine project, says it was “true news”—an attempt to protect the scientists in the hard-hit city.

In the United States, the Trump administration’s $10.8 billion Operation Warp Speed accelerated vaccine R&D faster than many researchers thought possible, specifically for the U.S. population. But an equally massive effort unfolded in China. CanSino and two other Chinese companies—one owned by the government, the other working closely with its regulatory agency—are investing substantial resources, testing four candidates in tens of thousands of volunteers around the world, and are likely only days or weeks away from announcing the outcomes of efficacy trials, just behind the encouraging early results announced over the past month by Pfizer and BioNTech, Moderna, AstraZeneca and the University of Oxford, and Russia’s Gamaleya Research Institute of Epidemiology and Microbiology.

But the low profile of those historic first injections, the military collaboration with a “private” company, and the ethically fraught decision to start with vaccinations outside of a clinical trial telegraphed that aside from the similar scale and speed, China’s vaccine effort is following a very different course from those in the United States and Europe. Most leading Western vaccines rely on sexy technologies such as genetically engineered viral vectors, designer proteins, and snippets of RNA. Three of China’s four leading vaccine candidates use an unfashionable stalwart: the whole inactivated virus, an approach that dates back to the first successful flu vaccine in the 1930s. And China’s vaccine effort is cursed by its dramatic success with aggressive public health measures to stop the spread of the coronavirus SARS-CoV-2, including forced isolation of cases and testing of entire cities. Whereas the raging pandemic in the United States has enabled trials there to quickly deliver signals of efficacy, “China crushed the coronavirus epidemic early, so they lost the opportunity to test the efficacy of their vaccines there,” says epidemiologist Ray Yip, who closely follows COVID-19 vaccine development as an adviser to Bill Gates. “If they had plenty of cases in China, they could have finished an efficacy trial ahead of other people.”

So China’s vaccine developers have gone abroad. Although the United States has shut them out of Operation Warp Speed, they have brokered deals with 15 other countries on five continents. They have mounted massive trials in the Arab world—and given candidate vaccines to top government officials there—and navigated toxic politics in Brazil, where the pandemic is raging fiercely, to test a vaccine and explore producing it there.

But China isn’t just seeking promising venues for clinical trials. Not urgently needing the vaccines at home to fight a virus it has largely quashed, it is playing a global game by pledging to send any proven vaccine to countries that are conducting trials for its candidates, or to share the technologies behind them. “They know they don’t need a vaccine to contain the epidemic in China,” Yip says. “They can take their sweet time.”

The Chinese company CanSino Biologics had the first COVID-19 vaccine to enter clinical trials, and by April had already progressed to a phase II study in Wuhan.

TPG/Getty Images

Yanzhong Huang, a global health specialist at both Seton Hall University and the Council on Foreign Relations, says the country is “actually using the vaccine to promote the diplomacy of foreign policy objectives.” This “vaccine diplomacy” he says, contrasts starkly with Warp Speed’s “vaccine nationalism” and aims to “fill in the void left by the United States.”

“It is a very carefully executed and carefully thought out strategy,” says Stephen Morrison, who directs the Global Health Policy Center at the Center for Strategic & International Studies. “A strategic goal of the Chinese government is to achieve hegemonic influence in the bioeconomy within the next decade.”

At home, too, attitudes toward vaccines contrast with those in the United States and Europe, where mistrust is high, Morrison says. To the consternation of vaccine experts overseas, hundreds of thousands of people in China have already lined up to receive the experimental vaccines—even before their value and safety have been proved. “There has not been a collapse of faith and trust in science and in the state,” Morrison says. “There’s less fear about where this is all going.”

The speed at which Chen and her colleagues were able to get those first shots is all the more remarkable given that CanSino was arguably slow off the mark.

Although some COVID-19 vaccinemakers launched their projects the day after the sequence for SARS-CoV-2 became public on 10 January, CanSino CEO Yu Xuefeng had reservations. “We started to look into it in the middle of January, but there was a hesitation,” he says. COVID-19, Yu worried, might be a blip, like severe acute respiratory syndrome (SARS), another coronavirus-caused disease, which alarmed the world in 2003 but disappeared a year later, after companies and governments had poured resources into developing vaccines.

Yu, who is originally from China, completed his Ph.D. in microbiology at McGill University in Canada in 1997, and then stayed, working on vaccines for nearly 9 years at a Sanofi Pasteur branch there. He co-founded CanSino—a portmanteau of Canada and China—in 2009. A team led by Chen back in China helped develop its only previous product to receive approval: an Ebola vaccine based on a widespread and largely harmless virus known as adenovirus 5 (Ad5), into which they stitched a gene for the surface protein of the Ebola virus.

Yu and his team considered making a COVID-19 vaccine with messenger RNA (mRNA) for the new coronavirus’ surface protein, called spike—the innovative approach taken by Pfizer and its partner BioNTech, the “winner” of the race to report preliminary efficacy data. But CanSino decided to go with what it knew, using the Ad5 vector to carry the spike gene. “I thought that’s the quickest and the mature way of developing a new vaccine,” Yu says.

In just 1 month, CanSino’s candidate was ready to be given to Chen and her team, and on 16 March the company launched the world’s first COVID-19 vaccine trial, in Wuhan, to test its safety and ability to provoke immune responses. CanSino had beaten Moderna by 8 hours—though a world transfixed by the vaccine race among Western companies paid little attention.

Several U.S. and European contenders, including AstraZeneca, have also adopted adenoviruses to carry the spike protein, some opting for an Ad5 vector similar to CanSino’s, despite several concerns about the approach. In 2007, two disastrous efficacy trials of an Ad5-based AIDS vaccine found that—for still-debated reasons—it actually raised the risk of HIV infection. The other worry is that preexisting immunity to Ad5 can attack the vaccine vector, which could explain why, in early trials, the CanSino vaccine elicited a weaker-than-expected antibody response. “We do see there’s some impact,” Yu concedes, “but it’s not black and white.” (The AstraZeneca/Oxford vaccine’s preliminary efficacy data suggest immunity against its adenovirus vector may have compromised that candidate’s performance, as well.)

China’s vaccine road trip

With few COVID-19 cases at home, Chinese vaccinemakers have had to test the worth of their candidates abroad and four are in efficacy trials in 15 countries.

PeruPeruPeruBrazilArgentinaArgentinaArgentinaMoroccoMoroccoMoroccoEgyptEgyptEgyptJordanJordanJordanTurkeyPakistanPakistanPakistanCHINABahrainBahrainBahrainUnited Arab Emirates (UAE)United Arab Emirates (UAE)United Arab Emirates (UAE)IndonesiaIndonesiaIndonesiaRussiaStart dateSizeCNBG*Morocco13 Oct. 16 July16 Sept.10 Sept.60045,00030006000ArgentinaPeruBahrain, Egypt, Jordan, UAECanSinoStart dateSizePakistan, Mexico,Argentina, Chile15 Sept.11 Sept.40,000500RussiaSinovacStart dateSizeTurkey14 Sept.10 Aug. 2 July15,00060013,060IndonesiaBrazil*Two branches of the China National Biotec Group (CNBG) are developing similar, but distinct, vaccines.ChileChileChileMexicoMexicoMexico

(GRAPHIC) N. DESAI/SCIENCE; (DATA) WORLD HEALTH ORGANIZATION; CLINICALTRIALS.GOV; CHINESE CLINICAL TRIAL REGISTRY; WCG CENTERWATCH

The two other Chinese players, Sinovac Biotech and China National Biotec Group (CNBG)—a subsidiary of one of the world’s largest vaccinemakers, the state-owned Sinopharm—are taking a different approach: vaccinating people with the w