A possible novel coronavirus vaccine jointly developed by Oxford University and Cambridge-based pharma AstraZeneca produced an immune response in test subjects during small scale phase-two trials, according to a study that appeared Monday in the science journal The Lancet.
It’s just the latest promising vaccine news as scientists all over the world scramble to come up with an effective tool to combat the coronavirus pandemic, which since first spreading in China in December has infected over 14.7 million people and killed more than 611,000 globally. But scientists The Daily Beast spoke with warned that the Oxford-AstraZeneca trials were small, rushed and, in the words of one infectious-disease expert, “ragtag.”
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Despite his criticism, Paul Offit, Director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, acknowledged that the United Kingdom vaccine candidate showed some promise.
The news out of the U.K. came the same day that The Lancet also published a study from a team of Chinese scientists reporting positive results from small-scale trials of a separate potential coronavirus vaccine from CanSino Biologics. Coming in the wake of positive early results on U.S. biotech company Moderna’s own vaccine candidate, the wave of data might make goals of a vaccine by early 2021 seem a bit less far-fetched.
But Offit and others stressed there’s a lot more work to do before the Oxford candidate or any other vaccine is ready for widespread use.
Does It Produce Antibodies?
The Oxford-AstraZeneca ChAdOx1 nCoV-19 vaccine is one of six that the U.S. government is backing as part of Operation Warp Speed, the feds’ $13-billion vaccine and therapy push. The U.S. government is also backing vaccine candidates from Moderna, Johnson & Johnson, Merck, Pfizer, and Novavax.
The ChAdOx1 nCoV-19 vaccine includes a harmless-to-humans adenovirus taken from chimpanzees. Scientists engineered the adenovirus, versions of which can cause cold-like symptoms, to include a spike protein like that on the SARS-CoV-2 pathogen. The theory is that the human immune system will recognize the protein and produce neutralizing antibodies to prevent infection by the actual novel coronavirus.
That theory held up in Oxford and AstraZeneca’s initial small-scale trials, which took place in between April and June. Researchers split a group of 1,077 test subjects at five locations in the United Kingdom into two roughly equal-sized groups. One group got MenACWY, a meningitis vaccine. The other got a single dose of the ChAdOx1 nCoV-19 vaccine candidate. Ten people from the latter group received a second dose of the coronavirus vaccine after 28 days.
Researchers drew blood from 35 subjects who received the novel coronavirus vaccine and tested the samples for antibodies and T-cells, which are pathogen-destroying white blood cells. The scientists were hoping for the same positive results they got when they tested the ChAdOx1 nCoV-19 on rhesus macaques monkeys earlier this year. The monkeys showed an immune response after a single dose.
All 35 human subjects who had their blood drawn in the recent trial had neutralizing antibodies and T-cells. The 10 people who got the booster dose had a lot more antibodies and T-cells. “This is exactly what we'd expect for a good vaccine at this point,” Stephen Jameson, a University of Minnesota immunologist, told The Daily Beast.
Do the Antibodies Actually Prevent Infection?
It’s much less clear that the vaccine works. It’s one thing for the immune system to produce antibodies, and it’s another for those antibodies to prevent people from getting sick.
Take Moderna’s vaccine candidate, which also produced antibodies in a small number of test subjects, according to a study published last week. Even in that case—with what the feds have described as their leading candidate—experts warned there was no surefire indication antibodies offered immunity.
And Offit expressed particular skepticism of the Oxford-AstraZeneca testing approach. For starters, why didn’t the Oxford-AstraZeneca testers look for antibodies and T-cells in all of the people who received the ChAdOx1 nCoV-19 vaccine-candidate instead of just 35? “What about those other 500 people?” he asked.
And why did the testers give a second dose of the vaccine to just 10 people? “You wonder whether their path forward is a two-dose vaccine,” Offit said. “If it’s a two-dose vaccine, they just published a study with 10 people.”
“It looks a little sloppy, frankly,” Offit said of the trial. Neither Oxford nor AstraZeneca responded to a request for comment.
Other experts were more bullish—if not on the certainty of antibodies conferring immunity, at least on the Oxford candidate’s baseline strategy.
“I think they were hoping it was a one-dose vaccine, and it looks like the two doses performed better,” Kawsar Talaat, a doctor of infectious diseases at Johns Hopkins Bloomberg School of Public Health, told The Daily Beast. Talaat said she was scheduled to join the research team for later trials of the Oxford-AstraZeneca vaccine.
Talaat stressed that even a small, imperfect trial is better than no trial when it comes to developing a coronavirus vaccine. “We all are incredibly eager for data.”
What About Side Effects, and How Long Does the Vaccine Seem to Last?
Researchers monitored all of the Oxford test subjects for adverse effects. They found that patients who received the coronavirus vaccine suffered worse fatigue and headaches than recipients of the meningitis vaccine did. The drug paracetamol helped to alleviate those symptoms, the Oxford study found.
These adverse effects were minor. Jeffery Klausner, a professor of medicine and public health at UCLA who previously worked at the Centers for Disease Control and Prevention, told The Daily Beast the Oxford-AstraZeneca vaccine appears to be “very safe.”
Still, it’s worth pointing out that while 91 percent of the test subjects in the Oxford trials were white, the novel coronavirus has disproportionately harmed people of color, at least in the United States. The Chinese vaccine candidate also appeared to work better in younger test subjects than it did in the older ones. The elderly, of course, are at higher risk from coronavirus infections.
As for durability, the Oxford results looked at the first 56 days of effects on subjects. The Chinese study didn’t look past 28 days. Obviously, with vaccine hopes often in search of years of protection, more study is needed.
How Far Are These Candidates From Actual Distribution?
There’s a lot of work left to do before Oxford and AstraZeneca—and the Chinese developers—can submit their vaccines to regulators for approval, much less manufacture them at scale. That said, the U.K. consortium has already begun large-scale, phase-three trials with 15,000 patients in the United Kingdom and Brazil. The Chinese scientists recommended the CanSino vaccine candidate enter phase-three trials “as soon as possible.”
Those trials should test whether the antibodies test subjects produce after receiving the ChAdOx1 nCoV-19 vaccine, or the Chinese vaccine, actually help to protect them from the novel coronavirus. In the case of the Oxford-AstraZeneca vaccine, the same trials could affirm that, as the phase-two trials hinted, the vaccine needs to be administered in two doses in order to be most effective.
“That is science,” Klausner said. “We learn as we go.”
