Science‘s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.
Brazil, with more cases of COVID-19 than any other country after the United States and India, is close to having its first licensed vaccine against the pandemic disease. At a press conference today, Brazilian researchers reported that a vaccine made by a Chinese company, Sinovac, was safe and had 78% effectiveness in preventing mild cases of COVID-19 in a study involving more than 12,000 health workers. It also completely prevented moderate and severe illnesses caused by SARS-CoV-2 infections, the team said. “The result we are seeing today is fantastic,” Rosana Richtmann, doctor from the Emilio Ribas Institute of Infectious Diseases in São Paulo, said at the press conference.
Dimas Tadeau Covas, director of the Butantan Institute – a state-owned vaccine maker in São Paulo that is co-sponsoring the trial – expects the Brazilian regulatory agency to clear the vaccine, called CoronaVac, for a emergency use in the next few days. “We now have all the documentation to make the request,” he said. Brazil also has ongoing efficacy trials on a COVID-19 vaccine made by AstraZeneca and the University of Oxford and many scientists expect it to also receive clearance soon. But the good news about CoronaVac has been clouded by complaints that the ad contained little data and that Sinovac had muzzled its Brazilian collaborators. Indeed, Brazilian researchers had previously held a press conference to announce that the vaccine was a success but were not authorized to give an exact figure of effectiveness.
Most of the vaccines licensed in other countries rely on high-tech approaches, such as messenger RNA encoding the SARS-CoV-2 surface protein, or the approach taken by the AstraZeneca-Oxford vaccine, which uses a harmless viral vector carrying the gene for this protein. But Sinovac turned to a more established approach. Its vaccine, which is also undergoing efficacy trials in Turkey and Indonesia, relies on the entire coronavirus, chemically paralyzed so that it cannot cause disease. The efficacy reported against mild disease is less than the approximately 95% obtained with two mRNA vaccines. But the “primary goal” of COVID-19 vaccines, Covas said, is to prevent those infected from progressing to serious illness. Another inactivated SARS-CoV-2 vaccine made by Sinopharm’s China National Biotec group has nearly identical results, the company reported last week from a large efficacy trial in several Middle Eastern countries. .
Sinovac and Sinopharm have been keeping tabs on what their partners may say about their vaccines. At the December 23 press conference held in São Paulo at the governor’s residence, researchers said that due to a contractual agreement with Sinovac, they could not declare CoronaVac to be more than 50% efficient, a internationally accepted standard for emergency clearance. Today’s presentation revealed the specific efficacy rate, but the researchers were hesitant to describe the exact number of people who developed disease in the vaccinated and placebo arms.
In an official presentation of the data to Butantan today, Covas made no mention of the number of cases, saying the data would be reported in a scientific publication and to Brazilian regulators. But pressed by reporters, he admitted there were 218 cases of mild illness. “The correct number is 160 something in the placebo group and less than 60 in the vaccinated group,” he said. (This would equate to 63% efficiency, not 78%.) CoronaVac appears to work just as well in the elderly as it does in other age groups, the researchers added.
The lack of data – not to mention the efficacy gap – predictably led to immediate skepticism. “Until they show us those numbers, it’s nothing more than an empty ad,” tweeted epidemiologist Denise Garrett, vice president of the nonprofit Sabin Vaccine Institute.
Details have also been scarce in announcements of initial efficacy testing by other manufacturers of COVID-19 vaccines. But a researcher who runs one of the 16 sites conducting the CoronaVac trial in Brazil, Esper Kallas of the University of São Paulo, said even the study’s investigators still didn’t know all the data. Kallas, who spoke with Science after the press conference, he said he was “happy” with the results. “We know the 78% are true.” But he’s frustrated that “we don’t have the granularity”. As for the case numbers mentioned by Covas, Kallas said: “I couldn’t understand these numbers.
Sinovac did not respond to Sciencerequest more information. But Kallas says the root of the disagreement between Butantan and Sinovac is what constitutes a confirmed case of COVID-19, as definitions may vary. The greater the number and severity of symptoms that a test subject must exhibit to be considered a case, the greater the efficacy of the vaccine appears to be. The Brazilian team and the vaccine maker were at odds over whether a case should show one or two recognized symptoms of COVID-19, in addition to a positive PCR test for the virus.
Researchers testing CoronaVac in Turkey apparently did not encounter such obstacles. On December 24, they revealed preliminary data showing 26 cases of COVID-19 out of 570 participants who received the placebo and 3 cases among the 752 volunteers vaccinated. This resulted in an efficiency of 91.25% and no serious safety issues emerged. The next analysis will take place in 40 cases, said Murat Akova, a researcher at Hacettepe University who is helping to conduct the study. Asked about the restrictions imposed on Brazilian researchers, Akova said there is “no such contract with Sinovac regarding the publication of data.”
The CoronaVac trial has been criticized by Brazilian President Jair Bolsonaro who has a strong bias against China and the vaccine itself and is a political rival to the governor of the state of São Paulo. But Sinovac, which has negotiated with the governor of São Paulo, will send Brazil enough vaccine for 46 million doses. (Two doses are needed for full protection.) Butantan has also started manufacturing the vaccine itself and hopes to produce around 1 million doses per day. Covas says the institute has started negotiations with several Latin American countries that want to get the vaccine.
Kallas, who has conducted around 15 clinical trials on different vaccines, says he’s never seen more aggressive attempts to control the release of the data, and fears they undermine a very positive message. “If you can prevent a person from being seen by a doctor 78% and avoid hospital admissions 100%, let’s toast and celebrate,” he says.