’t hesitate. “I just want this suffering to be over,” Domingues told Science.SÃO PAULO—Brazilian physical therapist Graziela Domingues is waging a life-and-death struggle against COVID-19. As head of the rehabilitation team at the Emilio Ribas Institute of Infectious Diseases hospital here, she helps COVID-19 patients in the intensive care unit exercise their lungs—all the while taking every possible precaution not to get infected and carry the virus home to her family. So when Domingues heard the hospital was recruiting volunteers for a COVID-19 vaccine trial, she didn
More than 6 months after the first COVID-19 case was confirmed in Brazil, the pandemic is still raging, now with about 30,000 new cases and 740 deaths daily. (The total death toll, 136,000, is second only to the United States’s.) Those grim statistics—along with a good medical infrastructure, vaccination expertise, a well-established regulatory system, and experience running clinical trials—have made Brazil an ideal place to put experimental COVID-19 vaccines to the test. At least four vaccine candidates, produced by Western and Chinese firms, are in trials here or soon will be. Negotiations are ongoing to test Russia’s Sputnik V vaccine as well.
Besides aiding the global struggle against the disease, the studies may also give Brazil earlier access to successful vaccines through deals that will allow the country to produce vaccines locally. “The more trials we can attract, the better,” says immunologist Jorge Kalil, a vaccine expert at the University of São Paulo, São Paulo.
Scientists worry, however, that high expectations and political promises may lead to premature vaccine approvals. At a press conference yesterday, for example, São Paulo state Governor João Doria went so far as to “guarantee” that the state would have vaccines for all its citizens by early next year and said “we will immunize you”—before acknowledging that the vaccine yet has to show its mettle.
Although case and death numbers in Brazil have begun to decline—and President Jair Bolsonaro is still downplaying the dangers of the disease—Brazilians have flocked to the trials. At the Emilio Ribas hospital, for instance, some 1500 people signed up for a trial of the Sinovac vaccine, nearly twice the number scheduled to participate at that site. Since July, the study—which is designed and run by Brazil’s Butantan Institute—has enrolled more than 4000 health care workers across 12 hospitals in six states; the target is 9000. “There is a waiting list” at every site, says Ricardo Palacios, clinical research director at the Butantan Institute. Half of the participants get Sinovac’s vaccine, which contains the killed coronavirus, and half got a placebo injection. (“I really hope I got the vaccine, and not the placebo,” Domingues says.)
In late June, Brazil became the first country outside the United Kingdom to begin to test a vaccine developed by the University of Oxford and AstraZeneca that contains a chimpanzee adenovirus genetically modified to express the SARS-CoV-2 spike protein on its surface. The project, run by the Federal University of São Paulo (Unifesp), is open to health care professionals and other groups with high exposure to the virus. It has enrolled 4600 people so far, out of 10,000 planned. More than 30,000 people offered to take part just in Rio de Janeiro and Salvador, according to the D’Or Institute for Research and Education (IDOR), responsible for running the trial in those two cities. “It completely maxed out our recruitment capacity,” says IDOR President Fernanda Tovar-Moll. The trial also plans to enroll 30,000 people in the United States, at least 10,000 in the United Kingdom, and 2000 in South Africa.
Trial leaders chose Brazil “because of the network of experienced and committed investigators who are able to support delivery of high quality clinical trials in the region,” Andrew Pollard, head of the Oxford Vaccine Group and chief investigator of the SARS-CoV-2 vaccine trials, wrote to Science in an email. “Everything is being done according to the most rigorous protocols,” says pharmacologist and Unifesp President Soraya Smaili. Along with other trials of the Oxford vaccine, this study was paused on 6 September, reportedly because a U.K. participant developed transverse myelitis; it resumed in Brazil and the United Kingdom on 12 September after independent safety monitors concluded the adverse event was unlikely to be related to the trial.
Meanwhile, the BioNTech/Pfizer/Fosun Pharma consortium is recruiting 2000 volunteers in São Paulo and Salvador for a phase III trial of its messenger RNA vaccine, part of a test program in 29,000 people that also has sites in the United States, Argentina, and Turkey. Johnson & Johnson’s Janssen vaccine was recently authorized to start to recruit 7000 volunteers in Brazil for its vaccine, which is also based on an adenovirus. The company also plans to run trials in the United States and seven other countries, with 60,000 participants in total, according to data on ClinicalTrials.gov.
The trials give Brazil early access to at least two vaccines. As part of its agreement with Sinovac, the Butantan Institute has won the right to produce 60 million doses of the company’s vaccine in Brazil by early 2021, while the Oswaldo Cruz Foundation (Fiocruz) will produce 30 million doses of the AstraZeneca vaccine by December or January 2021, and, if the clinical trial is successful, another 70 million in the first 6 months of next year. These first batches will be formulated and packaged using ingredients manufactured abroad by the two companies, but both agreements include technology transfer clauses that will eventually allow the vaccines to be fully produced locally if they are approved for clinical use.
Expectations among politicians and the public are high—especially for the Sinovac and AstraZeneca vaccines, which started earlier and recruited the most volunteers. “Everyone thinks the vaccine will be out in November, and by New Year’s we’re all going be out on the street [celebrating],” Kalil said in a videoconference with the Brazilian academies of science, medicine, and pharmacy on 17 September. “That would be ideal, but I don’t believe that’s going to be the case.”
Ricardo Gazzinelli, a Fiocruz vaccine researcher and president of the Brazilian Society of Immunology, worries public and political pressure may lead to premature approval in Brazil, paralleling similar fears in the United States. Releasing a vaccine without sufficient data about efficacy and safety could put people at risk and erode confidence in science, Gazzinelli says: “I think we need to be a little more cautious.”
Political rivalries in Brazil could add to the pressure. Fiocruz is connected to the federal government’s Ministry of Health, while Butantan is part of the São Paulo state government, and Doria is a political archenemy of Bolsonaro. Whoever gets a vaccine approved first may get the political accolades for it as well.
Already, there have been plenty of promises. Since the Butantan Institute announced its deal with Sinovac on 11 June, Doria and the Butantan Institute’s director, Dimas Covas, have said on several occasions they are confident the vaccine will be tested, approved, and available for mass distribution at the start of 2021. “I am very optimistic that January is a very realistic time frame,” Covas told Globo TV, Brazil’s biggest network, on 28 August. The Ministry of Health, which oversees Fiocruz, is working with a similar timeline. “January of next year we start vaccinating everybody,” Minister of Health Eduardo Pazuello said during an 8 September cabinet meeting.
COVID-19 vaccines will need authorization by the Brazilian Health Regulatory Agency (Anvisa), a well-regarded federal agency with a highly qualified technical staff. But Anvisa is not immune to political influence, as its chief is chosen directly by the president. Both Pazuello and Anvisa Director Antonio Barra Torres are military officers, appointed by Bolsonaro. So far, however, the agency has remained on good terms with scientists.
Domingues is hopeful for a good outcome, but says she realizes the shot in her arm may not protect her—if only because she might be in the trial’s placebo group. “I am very optimistic, but also very aware that I cannot let my guard down just yet,” she says.