- AstraZeneca and the University of Oxford released preliminary results of its COVID-19 vaccine trial.
- AstraZeneca/Oxford is the third team to release promising COVID-19 vaccine results this month.
- AstraZeneca’s average vaccine efficacy is above the 50 percent efficacy bar set by the Food and Drug Administration for COVID-19 vaccines.
An experimental COVID-19 vaccine developed by AstraZeneca and the University of Oxford has shown an average efficacy of 70 percent, according to early results from their phase 3 clinical trial released on Monday.
The results are based on two ongoing trials — one in the United Kingdom and the other in Brazil — involving more than 11,000 people. The trials used differing dosing strategies and saw different outcomes.
In the U.K. trial, study volunteers received a half dose of the vaccine followed by a full dose at least 1 month later. The efficacy was 90 percent.
Participants in the Brazil trial received two full doses at least 1 month apart, with an efficacy of 62 percent.
AstraZeneca/Oxford is the third team to release promising results this month. The Moderna/NIAID vaccine showed an efficacy of 94.5 percent, based on early results. The Pfizer/BioNTech vaccine had an efficacy of 95 percent, according to a final analysis.
Details of all three trials are limited, and none of the results have been peer-reviewed, so they should be viewed with some caution.
But the latest news opens up the possibility that at least three vaccines will be approved for use in the United States and other countries.
The AstraZeneca vaccine may be particularly useful in containing the COVID-19 pandemic in low- and middle-income countries because it’s cheaper and easier to store and transport than Moderna’s and Pfizer’s.
Many factors determine real-world effectiveness
AstraZeneca’s average vaccine efficacy falls below that of Moderna’s and Pfizer’s, but it’s above the 50 percent efficacy bar set by the Food and Drug Administration (FDA) for COVID-19 vaccines.
“The [AstraZeneca] results are very positive, especially since the vaccine can be stored under ‘normal’ conditions. Ninety percent is pretty good, but the 62 percent for the second tested regimen are not that impressive,” Florian Krammer, PhD, a virologist at Icahn School of Medicine at Mount Sinai, said on Twitter.
However, because full data from the phase 3 trials haven’t been released, it’s difficult to directly compare the vaccines.
In addition, real-world effectiveness is usually lower than the efficacy seen during trials. It can also be affected by many factors.
“My view? Don’t just focus on efficacy, 95 percent vs. 70 percent,” Dr. Peter Jay Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, Texas, said on Twitter.
“There will be other considerations: 1) durability or length of protection, 2) long term safety, 3) ease of delivery especially in [low- and middle-income countries],” he stated.
The first two are still unknowns for all three vaccines, with the answers coming from longer-term follow-up of vaccine trial participants.
As for ease of delivery, AstraZeneca may win out over the other two vaccines. The company’s vaccine can be stored and transported at normal refrigerated conditions for at least 6 months.
In addition, AstraZeneca’s vaccine will be more affordable to low- and middle-income countries. The price will be around $3 to $4 per dose, with the company pledging to offer the vaccine at cost through July 2021 and longer for low-income countries.
Pfizer’s vaccine will cost around $20, while Moderna’s will be $15 to $25, reported the Associated Press.
The AstraZeneca/Oxford vaccine already “accounts for more than 40 percent of the supplies going to [low- and middle-income] countries,” reported Bloomberg.
The United States is also expected to benefit from AstraZeneca’s vaccine, with 300 million doses secured for Americans as part of the federal government’s Operation Warp Speed.
More details needed about results
AstraZeneca’s results are based on 131 cases of COVID-19. No hospitalizations or severe disease occurred in people who received the vaccine, the company reported.
It also says no serious safety events were reported and the vaccine was “well-tolerated across both dosing regimens.” However, the company didn’t provide details on minor or moderate side effects experienced by study participants.
In addition, the company didn’t indicate how many people received the vaccine and how many received the inactive placebo. This information will be needed to know whether the efficacy results are statistically significant.
Also missing are details on how many participants were older or had one or more underlying medical conditions, such as diabetes, obesity, or heart disease.
The company, though, did publish data in The Lancet on November 18 from its phase 2 vaccine trial in older adults.
Researchers found that all age groups — including older adults without underlying medical conditions — developed antibodies against the novel coronavirus. This suggests that older adults may be equally protected.
Showing that the vaccine protects older adults is essential for two reasons. First, they’re at higher risk for developing severe COVID-19 and dying from it. Second, older adults can also produce less of an immune response to certain vaccines, usually due to the aging of the immune system.
The flu vaccine is an example of this, with older adults requiring a higher dose of the vaccine to be protected.
The AstraZeneca study offered one detail that the other two companies didn’t.
Participants swabbed themselves weekly for COVID-19 testing, even if they weren’t showing symptoms. Initial results based on this suggest that the vaccine also blocked asymptomatic infection, reported Nature.
Smaller first dose works better
Researchers aren’t sure why there was such a big difference between the two dosing regimens, but several possibilities have been raised.
“[The] simplest explanation is vector immunity,” Shane Crotty, PhD, a virologist at the La Jolla Institute for Immunology, said on Twitter.
The AstraZeneca/Oxford vaccine uses a cold-causing chimpanzee adenovirus — known as a vector — to deliver part of the new coronavirus’ DNA to the cells.
The cells convert the DNA into the virus’ spike protein, which the virus uses to infect cells. This triggers an immune response against the coronavirus, but because it’s just a small part of the virus, it doesn’t cause disease.
Complicating matters, the immune system also generates antibodies against the adenovirus. When the second shot is given, the immune system attacks adenovirus. This could reduce the vaccine’s efficacy.
The risk of this happening may be a “bigger problem with the higher dose, blunting [the] effectiveness of the booster immunization,” said Crotty.
The lower first dose in the U.K. trial resulted from a dosing error, reported Reuters. That means fewer people received that dosing regimen.
“That [U.K.] study is much smaller than other studies,” said Crotty, “and details were not provided (cases etc.), so I don’t make much of that number for now.”
AstraZeneca plans to ask the FDA to allow it to modify its trial in the United States to use the lower first dose. This would give it more data to see if the lower dose really produces a higher efficacy.
So far, the U.S. trial has enrolled around 10,000 participants. This trial was paused during the summer while the company investigated a suspected adverse reaction to the vaccine in a trial participant.
In October, the FDA authorized the company to restart the U.S. arm of the trial.
Even though its U.S. trial is ongoing, AstraZeneca plans to seek emergency FDA approval of its vaccine using data from its other sites.