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What’s next after mRNA vaccines?

Adenoviral vector and inactivated-virus vaccines for COVID-19 developed in China, India, Russia, and the UK are authorized in those countries, and beyond

by Ryan Cross
January 7, 2021 | A version of this story appeared in Volume 99, Issue 2


A photo of someone holding the AstraZeneca vaccine vial with a person in the background.
Credit: Oxford University News Office
The vaccine codeveloped by AstraZeneca and the University of Oxford was authorized for emergency use in the UK Dec. 30.

COVID-19 vaccine authorizations are ramping up worldwide. During the final days of 2020 and the first week of 2021, four vaccines developed in China, India, Russia, and the UK were granted varying degrees of approval in countries across Asia, Europe, and the Middle East.

The series of green lights follows the emergency use authorization of two messenger RNA (mRNA) vaccines in the US. Those shots were widely hailed for their high levels of efficacy—about 95%—and for undergoing a stringent and transparent regulatory review. In contrast, efficacy data for the four new vaccines are confusing, unpublished, or nonexistent. Scientists’ reactions to authorization of the shots are correspondingly mixed.

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One vaccine, based on adenoviral vector vaccine technology and developed by AstraZeneca and the University of Oxford, was authorized for emergency use in the UK and subsequently in several other countries, including India. Preliminary data from the Phase 3 study suggested that the vaccine’s efficacy may be as low as 62% or as high as 90%, depending on the dose regimen. Most people in the trial got the less effective dose; in fact, the more effective dose was given by mistake. AstraZeneca says the authorized dose is about 70% efficacious. There’s not enough data yet to authorize the more effective dose.

E. John Wherry, an immunologist at the University of Pennsylvania, notes that adenoviral vector vaccine technology has a longer history of safety in humans than mRNA vaccines, but AstraZeneca’s COVID-19 vaccine appears to be less effective than the mRNA vaccines, at least in the short term. “So it will be a tough sell if there isn’t an advantage in long-term efficacy or practicality,” Wherry adds.

In its favor, the AstraZeneca shot is significantly cheaper than mRNA vaccines and doesn’t require deep freezers for storage, notes Shailendra K. Saxena, a vice-dean and infectious disease scientist at King George’s Medical University in Lucknow, India. “The normal supply chain for vaccines that are currently in use across countries such as India can be used for supplying this vaccine, especially to the rural areas where cold chain logistics are weak,” he says in an email.

India authorized another vaccine, made by Bharat Biotech and based on traditional inactivated-virus technology. That decision has drawn more criticism from scientists, because in early January Bharat was still recruiting volunteers for its Phase 3 study of the vaccine. “It’s very opaque right now. There’s no peer-reviewed data at all,” says Carl Britto, a resident at Boston Children’s Hospital who studied at St. John’s Medical College in Bangalore, India.

In late December, Bharat posted a preprint study with results from a Phase 2 trial of 380 people. In January the company said the study is undergoing peer review and that other studies related to the vaccine will be published soon.

Britto is confident in Bharat, a well-known vaccine maker in India. “They are sticklers for doing things meticulously and following procedure,” Britto says, but he’s surprised that India would license a vaccine without peer-reviewed Phase 1 and 2 data. “Those are safety checks that shouldn’t be overlooked,” he says.

China granted emergency authorization to multiple homegrown vaccines last year, and on Dec. 31, the country granted conditional market approval to Sinopharm’s inactivated-virus vaccine. There are still no published Phase 3 data, but Sinopharm says the shot is 79% efficacious. The United Arab Emirates and Bahrain, which tested the vaccine, approved the shot 2 weeks earlier, claiming it is 86% efficacious.

An adenoviral vector vaccine developed by Russia’s Gamaleya National Center of Epidemiology and Microbiology was authorized for distribution in Argentina, Bolivia, Belarus, and Serbia in December and early January. Russia was the first to authorize it, back in August, on the basis of sparse Phase 1 data. In December, Gamaleya said the shot is 91% efficacious according to a Phase 3 study of 22,700 people, although that data haven’t been published yet.

Jung-Hyun Won and Howard Lee, from the Center for Convergence Approaches in Drug Development at Seoul National University in South Korea, say it is difficult to interpret the efficacy of these vaccines without more detailed information. “Approval in a country like China or Russia doesn’t guarantee approvals in other countries. We honestly don’t believe any EU nation or the United States would approve Sinopharm or the Russian Gamaleya institute vaccines with incomplete data,” they say in an email.

Steven Fiering, an immunologist at the Geisel School of Medicine at Dartmouth, cautions against making judgments. “This is an emergency situation,” he says. “So you can make the argument about the damage of waiting, or you could make the argument that it could be a disaster because you are putting this into a lot of people’s arms without having adequate data. But we don’t even have long-term data on the vaccines we’ve authorized either, so we’re cutting that corner. Different countries make different decisions based on their resources.”

The timing of the next vaccine authorization in the US is uncertain. AstraZeneca was a front-runner before its trial was temporarily halted in September because of a potential safety concern. The trial resumed in October and is still ongoing in the US. Moncef Slaoui, the head of Operation Warp Speed, the US COVID-19 vaccine effort, said it would likely take until April for an emergency use authorization.

Johnson & Johnson finished enrolling 45,000 people in its Phase 3 study of its adenoviral vector vaccine in mid-December and expects to request US Food and Drug Administration authorization in February. Novavax began a Phase 3 study of its protein nanoparticle vaccine in the US and Mexico Dec. 28. Since the FDA requires 2 months of safety data on the vaccine, authorization likely wouldn’t come until March at the earliest.

A vaccine from Sanofi and GlaxoSmithKline was delayed and will be starting a new Phase 2 study in February after an earlier study found the dose wasn’t high enough. The firms don’t expect to request authorization until the second half of 2021. Merck & Co. is developing two COVID-19 vaccines using different technologies, but the Phase 1 studies didn’t start until August and November.


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