Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.
In what has become a familiar pattern, the COVID-19 vaccine landscape has changed overnight, simultaneously raising hopes that more people may soon get vaccinated and triggering confusion. “It’s crazy,” says immunologist John Moore, a vaccine researcher at Weill Cornell Medicine. “Every morning, it’s just, 'What’s going on?'”
First, Beijing Biological Products Institute, a division of China National Biotec Group (CNBG), posted a brief announcement online that its vaccine had a 79.34% efficacy in a phase III study and was safe. The company, part of state-owned Sinopharm—one of the world’s largest vaccine manufacturers—said it is seeking approval from China’s regulatory agency.
While apparently good news, the statement left vaccine scientists clamoring for details. It said nothing about the number of trial participants, the rates of COVID-19 in the vaccinated and placebo groups, or even the locations of the trials. And it came three weeks after the health ministry in the United Arab Emirates (UAE), one country staging efficacy trials of the Sinopharm vaccine, issued a short press release that claimed 86% efficacy.
Then, the United Kingdom authorized emergency use of a vaccine made by AstraZeneca and the University of Oxford that had earlier caused perplexity after researchers reported efficacy results that combined trials with different populations, dosing of shots, and intervals between the prime and booster injections. Still more surprising, the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) said the booster shot could be delayed for up to 12 weeks after the primary shot. It explained that an “exploratory analysis” of some trial participants found that the vaccine efficacy was 73% after one full dose—a figure that, confusingly, was higher than the 62% after two full doses reported earlier in a study published in The Lancet. The delay would make it possible to give more people one shot quickly, a strategy that might bring down severe disease and death more quickly.
But some scientists questioned MHRA’s decision, wondering how much protection a single shot offers. “People are scratching their heads and going, 'Where are the data?'” Moore says. Biostatistician Natalie Dean of the University of Florida thinks the MHRA moved too quickly and without enough explanation of its decision. “Clearly there were deliberations that the U.K. had about this, but we don't have access to those discussions,” says Dean. “I think there's something lost in the process when we don’t have a really transparent approach.”
Still, COVID-19 vaccines are in short supply the world over, and both the Sinopharm report and the MHRA decision are likely to speed up immunizations. The AstraZeneca/Oxford collaboration hopes to make 3 billion doses next year, and Sinopharm has 100 million doses on hand and projects that it will produce 1 billion next year. “The news that the Sinopharm vaccine is effective is of course good news,” says epidemiologist Keiji Fukuda of the University of Hong Kong. “Having more vaccines to choose from is very welcome.”
CNBG has not announced pricing, but in an apparent bid to gain acceptance in developing countries, Chinese authorities have pledged to make vaccines available at “fair and reasonable prices,” possibly by subsidizing purchases. AstraZeneca/Oxford have set up a nonprofit that plans to sell its vaccine for as little as $3 per dose. The recently approved vaccines produced by Pfizer/BioNTech and Moderna, by contrast, cost roughly 10 times more, and the companies combined will have around 2 billion doses at most by the end of next year.
Their vaccines, which both rely on messenger RNA coding for a viral surface protein, present another obstacle for many countries: They require transportation at subzero temperatures. In contrast, the AstraZeneca/Oxford vaccine contains a harmless adenovirus engineered to shuttle the DNA for that same viral gene into the body, whereas the Sinopharm vaccine contains a chemically inactivated version of the entire virus. Both only require conventional refrigeration.
Thousands of Chinese citizens—including front-line health care staff, teachers, and public transport workers—already have received a Sinopharm vaccine under an emergency use authorization. Both the UAE and Bahrain have also issued an emergency use authorization for the vaccine.
“We are a little spoiled”
It’s not clear why the efficacy announced today for the Sinopharm vaccine is lower than the UAE claimed three weeks ago. And the paucity of detail in CNBG’s announcement perplexed some scientists. “I think that in America, rightly, you need to persuade the public that you're giving them a safe and effective vaccine, and in China, it's a somewhat different dynamic,” says Moore. “They just go, 'Look, the government has said it works so give me your arms.'”
“Most importantly we need to see the Phase III study results after peer review,” says Dale Fisher, an infectious disease specialist at National University of Singapore.
Kathleen Neuzil, an epidemiologist at the University of Maryland School of Medicine, is wary of science by press release but says, “There's no reason for me not to believe the Sinopharm announcement.” She stresses that the reported efficacy figures are well above the 50% cutoff that the U.S. Food and Drug Administration (FDA) set for emergency use authorization. “We have to remember that perhaps we are a little spoiled with the 95% we've seen with the mRNA vaccines,” says Neuzil, who co-runs a network of efficacy trials backed by the U.S. government’s Operation Warp Speed program that has invested some $11 billion in COVID-19 vaccine R&D.
Still, Neuzil says she is more confident about the AstraZeneca/Oxford results—in part because trial data have appeared in The Lancet. She also is on a scientific advisory board to the University of Oxford effort.
Waiting for a second dose
Several countries have debated whether to just give one shot for now of vaccines that have been tested in a two-dose regimen, in an attempt to provide more people with at least some immunity quickly. By endorsing a 12-week lag between the two doses of the Oxford/AstraZeneca vaccine, the MHRA is now the first regulatory agency to allow that.
Moncef Slaoui, the scientific head of Operation Warp Speed, has misgivings about that decision, noting that the data suggest “quite a lot of people” who receive the first dose of the Oxford/AstraZeneca vaccine did not develop robust immune responses. “The MHRA has taken quite significant risks,” says Slaoui, while stressing that he respects the agency’s expertise. “I wouldn't want to be sitting around for 12 weeks waiting for the second dose with the partially protective vaccine,” Moore adds.
The debate about increasing doses by expanding intervals is also playing out for the two mRNA vaccines already authorized for use in the United States. Warp Speed currently is only distributing half of its mRNA vaccine supply, as it wants to make sure it has enough on hand to give vaccinees their boosters on time—21 days after the first shot for the Pfizer/BioNTech vaccine and 28 days for Moderna. Stanley Plotkin, a veteran vaccine developer and an emeritus professor at the University of Pennsylvania, today co-authored an e-mail sent to Slaoui and several U.S. governmental officials asking them to consider using single doses as early as possible. Prioritization schemes would ensure that the most vulnerable people receive two doses on the proven schedule, they said, but for the general population, the standards could be relaxed. “We urge serious consideration of this step until supplies are adequate for two dose vaccination without leaving large numbers of susceptible individuals at risk,” the plea said.
Intervals between doses are somewhat arbitrary, says Paul Offit, a pediatrician at Children’s Hospital of Philadelphia and a member of an independent FDA vaccine advisory committee that discussed both mRNA vaccines. “You just pick a dosing interval,” says Offit, noting that two months is a standard gap. Because of the pressure of the pandemic, the mRNA vaccines were spaced more tightly.
Slaoui says there’s another way to double doses. Moderna has data showing that its vaccine stimulated a strong immune response in people under 55 years of age at half the dose being used, he notes. Cutting the dose in half for that age group—unlike increasing the interval between shots—“is both saving time and saving doses.”
*Update, 31 December 2020, 7:00 a.m.: China’s National Medical Products Administration announced today that it has granted conditional marketing authorization for the Beijing Biological Products Institute’s COVID-19 vaccine, one day after the company said it had filed an application to deploy the inactivated two-shot vaccine within China. An official with the National Health Commission said the COVID-19 vaccine, the first to gain regulatory approval in the country, “will be provided free of charge to all Chinese people," according to Xinhua News.
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