AstraZeneca and Oxford University on November 25 acknowledged a manufacturing error that is raising questions about preliminary results of their experimental COVID-19 vaccine.
A statement describing the error came days after the company and the university described the shots as highly effective and made no mention of why some study participants didn’t receive as much vaccine in the first of two shots as expected.
In a surprise, the group of volunteers that got a lower dose seemed to be much better protected than the volunteers who got two full doses. In the low-dose group, AstraZeneca said, the vaccine appeared to be 90 percent effective. In the group that got two full doses, the vaccine appeared to be 62 percent effective. Combined, the drugmakers said the vaccine appeared to be 70 percent effective. But the way in which the results were arrived at and reported by the companies has led to pointed questions from experts.
The partial results announced on November 23 are from large ongoing studies in the UK and Brazil designed to determine the optimal dose of vaccine, as well as examine safety and effectiveness. Multiple combinations and doses were tried in the volunteers. They were compared to others who were given a meningitis vaccine or a saline shot.
Frequently Asked Questions
A vaccine works by mimicking a natural infection. A vaccine not only induces immune response to protect people from any future COVID-19 infection, but also helps quickly build herd immunity to put an end to the pandemic. Herd immunity occurs when a sufficient percentage of a population becomes immune to a disease, making the spread of disease from person to person unlikely. The good news is that SARS-CoV-2 virus has been fairly stable, which increases the viability of a vaccine.
There are broadly four types of vaccine — one, a vaccine based on the whole virus (this could be either inactivated, or an attenuated [weakened] virus vaccine); two, a non-replicating viral vector vaccine that uses a benign virus as vector that carries the antigen of SARS-CoV; three, nucleic-acid vaccines that have genetic material like DNA and RNA of antigens like spike protein given to a person, helping human cells decode genetic material and produce the vaccine; and four, protein subunit vaccine wherein the recombinant proteins of SARS-COV-2 along with an adjuvant (booster) is given as a vaccine.
Vaccine development is a long, complex process. Unlike drugs that are given to people with a diseased, vaccines are given to healthy people and also vulnerable sections such as children, pregnant women and the elderly. So rigorous tests are compulsory. History says that the fastest time it took to develop a vaccine is five years, but it usually takes double or sometimes triple that time.
Did researchers mean to give a half dose?
Before they begin their research, scientists spell out all the steps they are taking, and how they will analyze the results. Any deviation from that protocol can put the results in question.
In a statement on November 25, Oxford University said some of the vials used in the trial didn't have the right concentration of vaccine so some volunteers got a half dose. The university said that it discussed the problem with regulators, and agreed to complete the late stage trial with two groups. The manufacturing problem has been corrected, according to the statement.
What about the Results Themselves?
Experts say the relatively small number of people in the low dose group makes it difficult to know if the effectiveness seen in the group is real or a statistical quirk. Some 2,741 people received a half dose of the vaccine followed by a full dose, AstraZeneca said. A total of 8,895 people received two full doses.
Another factor: None of the people in the low-dose group were over 55 years old. Younger people tend to mount a stronger immune response than older people, so it could be that the youth of the participants in the low-dose group is why it looked more effective, not the size of the dose.
Another point of confusion comes from a decision to pool results from two groups of participants who received different dosing levels to reach an average 70 percent effectiveness, said David Salisbury, an associate fellow of the global health program at the Chatham House think tank.
You've taken two studies for which different doses were used and come up with a composite that doesn't represent either of the doses, he said of the figure. I think many people are having trouble with that.
Why would a smaller first dose be more effective?
Oxford researchers say they aren't certain and they are working to uncover the reason.
Sarah Gilbert, one of the Oxford scientists leading the research, said the answer is probably related to providing exactly the right amount of vaccine to trigger the best immune response.
It's the Goldilocks amount that you want, I think, not too little and not too much. Too much could give you a poor quality response as well, she said. So you want just the right amount and its a bit hit and miss when youre trying to go quickly to get that perfect first time.
What are the next steps?
Details of the trial results will be published in medical journals and provided to UK regulators so they can decide whether to authorize distribution of the vaccine. Those reports will include a detailed breakdown that includes demographic and other information about who got sick in each group, and give a more complete picture of how effective the vaccine is.
Moncef Slaoui, who leads the US coronavirus vaccine program Operation Warp Speed, said Tuesday in a call with reporters that US officials are trying to determine what immune response the vaccine produced, and may decide to modify the AstraZeneca study in the US to include a half dose.
But we want it to be based on data and science, he said.Follow our full coverage on COVID-19 here.