A Covid-19 vaccine being developed by Oxford University and the drug giant AstraZeneca generated an immune response in a study of roughly 1,000 patients, according to interim results published Monday.
The data, published in the medical journal the Lancet, also show that the vaccine caused side effects, including fever, headaches, muscle aches, and injection site reactions, in about 60% of patients. All of the side effects were deemed mild or moderate, and all resolved themselves over the course of the study.
While the Oxford-AstraZeneca vaccine, known as AZD1222, has moved most rapidly into larger-scale studies of any major contender — and AstraZeneca has said that billions of doses could be manufactured — the new data represent the first glimpse researchers have gotten at its efficacy. They show a relatively safe vaccine — though side effects were greater than for a meningitis vaccine, to which it was compared — that engages the immune system to fight the virus. AstraZeneca said that, because of the results, it is likely that future studies will test giving patients two doses of the vaccine.
“At the end of the day, you have to prioritize efficacy and then resolve the challenges around the logistics of the trial or logistics of manufacturing large quantities of vaccine,” said Pascal Soriot, AstraZeneca’s CEO, in a briefing with reporters.
The Lancet also published results of another vaccine, from the Chinese biotech CanSino, that had been previously released. The Phase 2 results showed that, as was seen in the Phase 1 data, the vaccine induced neutralizing antibody responses — which could be vital to preventing the disease’s dangerous symptoms — in most subjects. But further study continues to show that this vaccine works better in some people than others. And among those it didn’t work as well in were people aged 55 and older, a key target for Covid-19 vaccination.
“The results of both studies augur well for phase 3 trials, where the vaccines must be tested on much larger populations of participants to assess their efficacy and safety,” wrote two vaccine researchers from Johns Hopkins University, Naor Bar-Zeev and William Moss, in an accompanying editorial.
Added Michael Ryan, the World Health Organization’s health emergencies chief: “We now need to move into larger scale, real-world trials, but it is good to see more data, more products moving in to this very important phase of vaccine discovery.”
The data on the Oxford-AstraZeneca vaccine do not provide enough information to predict whether it will be more effective than other vaccines that are also entering clinical trials.
AZD1222 is one of 23 potential Covid-19 vaccines that are being tested in clinical trials, according to the World Health Organization. Studies in which thousands of volunteers are given either a vaccine or placebo are necessary to know for sure if any vaccine prevents infection with SARS-Cov-2, and how well that vaccine works. No such studies have been completed.
All of the volunteers who received the vaccine developed neutralizing antibodies against Covid-19. However, participants who got a single injection of the vaccine did not produce significantly more antibodies than those who had recovered from Covid-19.
The vaccine also produced a response in T cells, a type of white blood cell that attacks cells infected with viruses, according to the paper. In a statement, Andrew Pollard of the University of Oxford, the study’s lead author, said that the vaccine is intended to induce both types of responses. “We hope this means the immune system will remember the virus, so that our vaccine will protect people for an extended period,” he said.
In the Oxford trial, participants were between the ages of 18 and 55 and split roughly 50-50 between male and female. Ninety-one percent of volunteers were white, while roughly 5% were Asian, and fewer than 1% were Black.
The vaccine has already entered large-scale tests, known as Phase 3 trials, aimed at proving its efficacy. It will also be part of the large trials being conducted in the U.S. as part of the government-run program known as Operation Warp Speed.
Two other potential vaccines, which use a technology called messenger RNA that takes advantage of the body’s genetic messaging system to provoke an immune response, released preliminary results earlier this month. The vaccines, developed by Moderna, a Massachusetts biotech firm, and the team of the German firm BioNTech and the drug giant Pfizer, both increased levels of neutralizing antibodies in patients. Both also caused side effects, including fevers, in many patients. Both are set to start late-stage efficacy studies later this month. In a paper also released Monday, BioNTech and Pfizer said their vaccine also induced T-cell responses.
Mene Pangalos, an AstraZeneca executive vice president, warned during the company’s briefing that it is “almost impossible” to compare antibody levels between different vaccines because of variation in the tests used to measure them. He pointed out that AZD1222 has another advantage: it needs to be kept cold, but not frozen, as the messenger RNA vaccines do.
AZD1222, which was developed by researchers at Oxford’s Jenner Institute, works differently, by using a genetically engineered virus, called adenovirus, which was taken from chimps and modified not to replicate and sicken people. It carries a gene for one of the proteins in SARS-Cov-2 and inserts it into a recipient’s cells. The virus causes the patient’s cells to make that protein, which is then recognized by the immune system as foreign. This results in an immune response.
The platform has not been used in an approved vaccine. But it has been used in experimental vaccines against the viruses that cause other outbreaks, including the Ebola virus and the virus that causes Middle East respiratory syndrome (MERS). That work left the Oxford group ready when SARS-CoV-2, a related virus, became a threat.
In a statement, Sarah Gilbert, a professor at the University of Oxford who has been a key figure in developing the platform, known as ChAdOx1, said the data, though early, showed promise.
“If our vaccine is effective, it is a promising option as these types of vaccine can be manufactured at large scale,” Gilbert said.
Researchers at the National Institutes of Health found that AstraZeneca/Oxford vaccine protected monkeys against SARS-CoV-2, although the protection did not completely prevent the virus from being detected living in the animals’ respiratory tracts. Those results led to the April 23 start of the clinical trial in people that is being released on Monday.
AstraZeneca and Oxford announced their partnership on the vaccine on April 30. A 10,000-patient study testing the vaccine is being run in the United Kingdom, and a separate 5,000-patient test began in Brazil in June. Soriot, the AstraZeneca CEO, said that phase 3 results could become available in September, October, or November.
CanSino, for its part, is now planning for a Phase 3 trial. Its vaccine is what’s known as a viral vector vaccine; it uses a live but weakened human cold virus, adenovirus 5 — known as Ad5 for short — as a delivery system that teaches the immune system to recognize the SARS-CoV-2 coronavirus.
Many people have had previous infections with adenovirus 5, raising concerns that the immune system would focus on the Ad5 parts of the vaccine rather than the SARS-Cov-2 material fused to it. Many research groups that work on viral-vectored vaccines stopped using Ad5 because of concerns about preexisting immunity, which can run to 70% or higher in some populations.
The data released Monday showed subjects in the Phase 2 trial who had no or low-level pre-existing immunity to Ad5 developed neutralizing antibodies to SARS-CoV-2 at roughly double the rate of people who had high-level preexisting immunity. High-level preexisting immunity was more common in people in the study aged 55 and older. The researchers said the vaccine’s response in older adults will be studied in a Phase 2b trial.
The findings concern some experts. Gary Kobinger, director of the Infectious Disease Research Center at Laval University in Quebec, questioned whether it makes sense to pursue development of the vaccine, given the problem with preexisting immunity to the Ad5 vector, and the relatively high rate of adverse events seen in the study. Most of the grade 3 reactions — the most severe — were seen in people who received the highest of two doses used in the study, though there was one report of a grade 3 fever in a person who received the lower dose. CanSino has dropped the higher dose.
But Kathryn Edwards, scientific director of the Vanderbilt Vaccine Research Program in Nashville, Tenn., noted the world is going to need as many Covid-19 vaccines as can be made. The CanSino vaccine may not be protective enough for older adults, she said, but it might be useful in children. To date the vaccine has only been studied in people 18 years and older.
The CanSino researchers suggested the dampening of the immune response due to preexisting immunity to the Ad5 vector might be overridden by using a booster dose sometime between three and six months after the original dose — a potentially awkward dosing regimen that would not deliver rapid protection in the people who are at highest risk from Covid-19, older adults. Edwards said, though, that another dose might simply boost the immune response to the Ad5 vector, not the intended target, SARS-CoV-2.
The CanSino vaccine has already received an emergency license in China for use in the military.
This story was updated with quotes from AstraZeneca, the WHO, and outside experts.
I am 71 cancer survivor hpv last year and I am very intrested in being involved in the study,of the covid-19 vaccine . A Vietnam era veteran.
Interesting that all AstraZeneca’s volunteers, so far, have been 18-55. As the hardest hit Covid patients are older (the older, the worse affected!), I wonder when they will get round to testing the vaccine’s efficacy in the older age groups? I hope we will not end up with a vaccine which protects those who would, generally, have managed quite well without it, but not helping those most in need.
I am concerned that not enough people of color (Africans, African Americans or Latinos are a part of the testing. So how did it work on people of color that were tested. Do you intend to test more people of color. Black and Brown people are a larger group than White people, yet Black and Brown people are a very small part of the research for this vacine.
Yes, more people of color need to be included in these efforts. However, underrepresentation of Blacks and Latinos in clinical research is a common concern, largely rooted in stigma, racism, and mistrust of the healthcare system at large. It may simply be difficult for researchers to recruit willing participants from those demographics. Likewise, Latinos – non-Enlish-speakers, in particular – are less likely to be made aware of clinical trials by their providers. While I’d very much like to see trials for a COVID-19 vaccine take place among more people of color, there are many layers to the lack of trials among them that need to be addressed.
Congratualations Mr. Pascal Soriot, CEO, Astragenecaa for your kind efforts in favor of human being by producing AZD1222. We are Bangladesh awaiting to get it in our hand to protect corona . Appreciate respond with your views on it. Best wishes.
I have yet to read any article about R&D on correllation or relevance of PRIOR VACCINATIONS (what type, how often, how recent). Ad5 pre-conditioned immunity indicates that prior (flu) shots do make a difference. Older people and health care workers get flu shots more often – and they are the most Covid infected. Is there a link ?? Or if they “do great” : what prior inoculations do they possibly have in common? When is this finally being researched ??
The Need of second.
Go ahead. God bless all of you.
both these vaccines use viruses (adenovirus and adeno-associated virus) to deliver the spike gene into host cells for display and recognition by the immune system, is that right (ie. like gene therapy). One big problem is that most of the population has developed immunity to both adenovirus and adeno-associated viruses (mostly benign viruses). So we already have in place defenses against the delivery systems (the same problem exists for gene therapy). It would be great if STAT could dig a little deeper in both explaining the platforms and their weaknesses….I wouldn’t buy any stock.
They are using the chimpanzee adenovirus. They say that in previous tests, humans have shown no evidence of antibody. It looks as if the test of the adeno 5 vaccine was run in indivuals with no pre-existing antibody. So we dont now if that will be an issue in the general population, where some probably do have Ad5 antibody. Re adenovirus and AAV for delivery, there have been problems in the past with these vectors when used in gene therapy protocols. The most notable was the death of Jesse Gelsinger when he received a gene therapy vaccine using an adenovirus as a vector. They say that these vectors have now been modified with CRISPR technology to render them harmless as pathogens. Moreover they are counting on the weak immunogenicity, if any, of the AAV. It has not been historically a potent antigen in humans. We shall see. Proceed with caution.
“It carries a gene for one of the proteins in SARS-Cov-2 and inserts it into a recipient’s cells”
I believe that’s grossly incorrect!
It should be the simian adenovirus is engineered to express the S protein on it’s surface, therefore acting like a mock up of the SARS-CoV-2 virus, a carrier of the S protein.
I think what they probably mean is that the engineered virus inserts itself into the recipient’s cells and replicates. The released virus provides additional immunogenic stimulation to spike protein above and beyond the initial injection. You are correct, the statement is poorly worded and should be modified.
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