Oxford Vaccine A True Game Changer?
Following a series of recent steps forward in the race to develop an effective Covid-19 vaccine, attention is turning to the much-anticipated results from trials of Oxford University’s candidate.
The UK has so far purchased 40 million doses of the vaccine developed by US pharmaceuticals giant Pfizer, and has also rushed to reserve five million of Massachusetts based Moderna’s candidate, after both were found in late-stage trials to have an efficacy of more than 90%. But “Britain has the most riding on the inoculation being developed by Oxford University and AstraZeneca - of which it has reserved 100 million doses”, The Guardian reports.
A source at the Department of Health and Social Care told the newspaper that the first results from the Oxford trials are “imminent” and that provided approval is granted by regulators, the jab could be one of the first of the 200-odd being developed worldwide to be rolled out.
At what stage of development is the Oxford vaccine?
The Oxford University vaccine, made in partnership with Cambridge-based company AstraZeneca, has long been a front runner in the contest to find a coronavirus jab.
In early September, trials of the vaccine resumed after being briefly paused as a result of a reported side effect in a patient in the UK. The jab is currently in Phase 3 testing that has involved “some 30,000 participants in the US as well as in the UK, Brazil and South Africa”, the BBC reports.
Although Phase 3 trials can take several years, Politico London Playbook’s Alex Wickham confirms that “government officials expect positive news soon and for it to be ready for rollout alongside the Pfizer jab in December”.
How does the jab differ from the other candidates?
While the Oxford vaccine – called ChAdOx1 nCoV-19 – “uses a different technology from the Moderna jab, the two vaccines both rely on stimulating cells to produce a specific protein, which in turn triggers an immune response – meaning Moderna’s results bode well for Oxford”, The Guardian reports.
But unlike the Oxford jab, those developed by Modena and Pfzier use messenger ribonucleic acid, also known as messenger RNA, or mRNA.
Conventional vaccines are produced using weakened forms of a virus, but mRNAs use only the genetic code of the virus. In the Covid vaccines, the mRNA carries instructions for making the spike protein that protrudes from the outside of the coronavirus cell.
Once injected, the vaccine causes “protein-making machinery within the human cells to churn out this spike protein”, prompting the immune system to go into defence mode, the paper explains.
By contrast, the Oxford version is a conventional vaccine, using a harmless, weakened version of a common virus that causes colds in chimpanzees. Researchers have previously used this technology to produce vaccines against pathogens including flu, Zika and Middle East Respiratory Syndrome (Mers).
And the Oxford team are now using the “harmless chimp cold virus to deliver genetic information from the coronavirus to human cells to trigger the production of the spike protein” that kick-starts the immune response, says The Guardian.
So will it end the pandemic?
Professor Andrew Pollard, director of the Oxford Vaccine Group, told The Guardian that “the positive results from the other developers means it is likely that there will be multiple vaccines on target, which is great news for the world”.
But concerns persist over how long the vaccine protection will last. Since the Oxford jab “uses a live chimpanzee adenovirus to transport elements of Sars-Cov-2 into humans, it’s expected people will develop immunity to the viral vector, preventing the vaccine from being used for future top-ups”, The Independent reports.
“For a scenario where the Oxford vaccine gets rolled out across the UK, that might give people protection for six months to a year,” Professor Robin Shattock, who is leading a separate team of vaccine researchers at Imperial College London, told the paper. “But you then need something to come back and reboost people.”
Shattock believes that his vaccine could be used as a regular booster for maintaining immunity. And that could offer “a permanent route out of the pandemic”, The Independent suggests.
Fauci: Moderna Vaccine Results Are 'Important Advance,' But Virus Precautions Are Still Vital
Dr. Anthony Fauci, the country's foremost infectious disease expert, tells NPR that it's "OK to celebrate" the good news about Moderna's coronavirus vaccine, but warned it's not the time to back off on basic health measures.
The biotechnology Moderna Inc. said Monday that its experimental vaccine was 94.5% effective in preventing the disease, according to data from its clinical trial.
"From a scientific and potential public health standpoint, this is an extraordinarily important advance," Fauci told Rachel Martin on Morning Edition Tuesday.
The Moderna study has 30,000 volunteers who either got a placebo or the vaccine. There have been 95 people who happened to get sick with COVID-19. But 90 of the people who got sick didn't get the vaccine; of people who got vaccinated, only five got sick.
A week earlier, Pfizer said its vaccine was more than 90% effective in its own trial.
The Food and Drug Administration set a minimum effectiveness of 50%. Fauci said a few months ago he would "like [a vaccine] to be 75% or more" effective. So the news of two vaccines showing early results of being 90% or higher "is a very, very important advance in our armamentarium of trying to stop this outbreak," Fauci said Tuesday.
Moderna said it will ask the FDA to approve its vaccine for emergency use "in the coming weeks" while a Pfizer partner said it could apply as early as this week.
The timeline is significantly quicker than the standard drug approval and distribution process. It's helped by the government's Operation Warp Speed, which has already paid companies billions of dollars to start making vaccines before they are approved.
Fauci said that hopefully by the end of the year, two companies' vaccines will have enough doses available for 20 million people.
"At best, what we will see, will that be some people — generally the highest priority, that's determined by an advisory committee and ultimately the CDC — there will likely be some getting vaccinated towards the end of December," he said.
The consensus is that health care workers will be the first ones to get vaccinated.
"As we get into January, February, those doses will increase," Fauci said. At that point, doses will still be limited to certain prioritized groups.
"By the time you get to, let's say, the end of April, the beginning of May, June, July, as we get into the second quarter, it'll be much more likely that you'll have, quote, 'the general population' that's not on the priority list will be able to get vaccinated," he said.
There's also the challenge of convincing people to get vaccinated once they can. In one poll in August, 35% of respondents said they wouldn't get a coronavirus vaccine once it becomes available.
Fauci says he hopes that people "who are hesitant or reluctant" to get vaccinated might be persuaded "when they see the extraordinary efficacy of the vaccine."
Still, that is many months away. In the meantime, the Trump administration has not coordinated with incoming members of President-elect Joe Biden's team on coronavirus response. Biden said on Monday: "More people may die if we don't coordinate."
Fauci, who sits on the current White House coronavirus task force, noted that he's worked with six presidential administrations. He said transitions are "critical."
"I would like to see the interaction with people who might be coming in and be doing the things that are being done now by the task force and by the people in the health system," he said.
Despite lack of coordination with the current White House, the Biden team is already talking with vaccine manufacturers, which Fauci called a "good thing."
The eventual vaccine is "not going to do it alone, though," he said. "That's the important point. This should not be a signal to pull back on the public health measures that we must continue to implement."
As part of that, health experts are warning that traveling for Thanksgiving next week is fraught with risk as coronavirus cases soar nationwide.
"If you have people in the family who are at a higher risk, people that might be elderly with underlying conditions and you want guests to come in that might be going through crowded airports or on airplanes, you really got to think twice," Fauci said. "Is this something that I really want to take a risk for?"
Fauci, who is 79, said his three daughters who live in different parts of the country aren't coming home for Thanksgiving this year. They'll spend some time talking on video calls instead.
"I don't like it that way, but I think they're making a prudent decision and trying to protect their father, and I'm proud of them for that," he said.
Moderna's COVID-19 Vaccine Shines In Clinical Trial
A second COVID-19 vaccine now also appears highly effective in preventing illness following exposure to the virus that causes the disease.
The biotech company Moderna Inc. said Monday that its experimental vaccine was 94.5% effective in preventing disease, according to an analysis of its clinical trial.
The news comes a week after Pfizer and BioNTech said their vaccine was more than 90% effective.
The results for both vaccines come from interim analyses of large clinical studies. In the Moderna study there were 30,000 volunteers. Half got two doses of the vaccine 28 days apart; half got two shots of a placebo on the same schedule.
There were 95 instances of COVID-19 illness among the study participants; only five of those cases were in the vaccinated group. Ninety were in the group receiving the placebo. Of these, there were 11 cases of severe disease. The results indicate the vaccine was inducing the kind of immune response that protects people if they were exposed to the coronavirus.
"This positive interim analysis from our Phase 3 study has given us the first clinical validation that our vaccine can prevent COVID-19 disease, including severe disease," Stéphane Bancel, chief executive officer of Moderna, said in a statement.
Both the Moderna and Pfizer vaccines use the same technology to make their vaccines. It's based on a molecule known as mRNA, or messenger RNA. That molecule contains genetic instructions for making proteins inside cells.
For the vaccine, researchers created an mRNA with the code for making the coronavirus spike protein. The protein is the key to the virus infecting cells. It's also what can trigger someone's immune system to make antibodies against the virus, but without causing infection since the rest of the virus is missing.
That two mRNA vaccines appear to be working is remarkable, since the technology is new and there hasn't been an mRNA vaccine approved by the Food and Drug Administration made to date.
The Moderna and Pfizer studies were conducted using slightly different protocols. To be counted as a COVID-19 case, participants in the Moderna study had to have at least two symptoms of disease in addition to a positive test for the virus. The Pfizer study required only one symptom. Also, Moderna waited 14 days following the second injection to begin counting cases; Pfizer's study started counting at seven days.
The vaccines also differ in their storage requirements. Moderna says its vaccine can be safely stored in freezers at about 25 degrees Fahrenheit (minus 4 degrees Celsius), a temperature easily reached by a home refrigerator freezer. Pfizer's vaccine required storage in specialized ultracold freezers capable of cooling below minus 94 degrees Fahrenheit (minus 70 degrees Celsius). Moderna also says its vaccine will remain potent for up to 30 days at normal refrigerated temperatures, which should ease distribution.
Both companies' vaccine studies managed to recruit a reasonably diverse group of people. Moderna reports 6,000 enrollees who identified as Hispanic or Latinx and more than 3,000 participants who identified as Black or African American, as well as 7,000 people older than 65, and 5,000 with high-risk chronic diseases.
Pfizer and Moderna are still gathering safety data the Food and Drug Administration has said is necessary for consideration of an emergency use authorization that would allow the companies to distribute the vaccine during the pandemic.
Side effects seen for the Moderna vaccine at the interim analysis included pain at the injection site, fatigue and aching muscles and joints. The data safety and monitoring board didn't identify "any significant safety concerns."
Moderna said it intends to file "in the coming weeks" with the FDA for authorization of the company's vaccine for emergency use.
The federal Operation Warp Speed project to hasten development of COVID-19 vaccines awarded Moderna a $1.5 billion contract in August to ramp up manufacturing and deliver 100 million vaccine doses, enough for 50 million people. The government has an option to buy up to 400 million more doses.
Moderna said Monday that it expects to be able to ship about 20 million vaccine doses in the U.S. by the end of 2020. Next year, the company said it expects to be able to make 500 million to 1 billion doses worldwide.
The research and development of the Moderna vaccine was aided by $955 million in federal funding from the Biomedical Advanced Research and Development Authority. Moderna has also been developing this vaccine alongside the National Institute for Allergy and Infectious Diseases, which in July told NPR it expects to spend about $410 million on the effort.
Pfizer vaccine results are promising, but lack of data ‘very concerning,’ experts say
While the news of high efficacy is thrilling and has exceeded expectations, several researchers have flagged some vital unknowns.
The world cheered this week after pharmaceutical companies Pfizer and BioNTech announced early findings from their phase three trial for a frontrunner COVID-19 vaccine. On November 9, the companies issued a news release claiming their vaccine candidate effectively prevented infection with the coronavirus—welcome news after soaring global cases have prompted new shutdowns and warnings of intensive care units filled to capacity.
But even more stunning was the extent the vaccine exceeded industry expectations. According to their press release, data reviewed by an independent panel of experts show the vaccine to be 90-percent effective, meaning nine out of 10 recipients experienced some sort of benefit—far surpassing the 50-percent benchmark set by health overseers such as the U.S. Food and Drug Administration and the World Health Organization.
The news was unprecedented because it appears to be a vindication of the mRNA technology that so far has only been proven in animal models. But it was also surprising because the companies took the unusual step of releasing some of the results—what they called an “interim report”—before the rest of the data was available.
“As a scientist, you’d want to see actual data from a clinical trial to really know what the actual interpretation of the results are,” says Aliasger K. Salem, chair of pharmaceutical sciences at the University of Iowa.
Several experts say they’re concerned that the public is getting an incomplete picture about the vaccine’s success that doesn’t reveal critical information, such as which demographic groups it protected and whether it was from a mild or severe form of the virus. There’s also the real possibility that the 90-percent figure could change as the trial ticks on and investigators collect more results. Plus, the unpublished results have not been peer-reviewed or even released as a preliminary preprint.
“The lack of data is very concerning,” adds Peter Doshi, associate professor of pharmaceutical health services research at the University of Maryland School of Pharmacy. “All we have right now is a headline by Pfizer.”
Yet others praised the decision—saying that it’s unlikely the 90-percent result would change significantly in the meantime. “It probably will shift, but it might be 87. But given the numbers they have in the trial, it can’t be 50 percent,” says Robert Wachter, chair of the University of California, San Francisco, department of medicine who studies patient safety. “It’s clearly in the range of 90.”
Nuts and Bolts
Here’s how the Pfizer-BioNTech vaccine trial works. The third and final phase began in July, when investigators evenly assigned 43,538 participants to two groups: one to receive the vaccine being studied, and another to get an inactive substance known as a placebo. According to the trial’s protocol, the vaccine comes in two doses, which are given three weeks apart. The researchers waited at least seven days after the second dose had been administered to see who contracted COVID-19 in real life, assuming each group practiced comparable risk-taking behaviors.
To keep the process unbiased, drug companies are typically “blinded” during phase three to what’s happening on a day-to-day basis in terms of results. But the COVID-19 vaccine trial comes with exceptions—milestones based on how many cases have been recorded among the volunteers. Once hit, the independent panel—known as a data monitoring committee—can tell the companies how things are going. Pfizer and BioNTech could make this announcement now because the trial reached one of these milestones, documenting 94 cases of COVID-19.
Yet the preliminary data doesn’t reveal which of these infected patients received the vaccine and whom it failed. It also doesn’t involve all the trial participants but rather an undefined subset, though Wachter says his best guess from the press release is the vaccine group recorded about nine COVID-19 cases, while the placebo arm experienced about 90.
The risk of not reporting these complete results is that the headline could send a misleading message that “the vaccine provides greater benefit than it really does,” says Doshi, who studies the drug approval process. “Pfizer hasn’t released anything indicating that this 90-percent effective statistic applies to those most frail, like older adults or those in nursing homes who are at highest risk.”
It’s also unclear if the vaccine simply prevented symptoms in mild or moderate cases, or if it reduced severe outcomes. Such information is critical because a vaccine ideally would reduce the number of deaths, hospitalization, and ICU visits. “The studies should give us a sense of severity, but they’re only looking at symptoms,” says Maria Elena Bottazzi, co-director of the Texas Children’s Hospital Center for Vaccine Development in Houston.
It’s also unknown whether any of the 94 coronavirus patients had underlying risk factors. That data matters because state and county officials are prioritizing high-risk and socially vulnerable groups during the first distribution waves. “It’s not clear in the trial who got the vaccine,” says Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA’S COVID-19 advisory committee. “You wonder whether those groups of people were adequately represented.”
The home stretch?
News of the announcement boosted stock markets, helping reverse a downturn witnessed over recent weeks. But this reaction also raised questions of why Pfizer and BioNTech decided to release this interim data? When asked if Pfizer was under pressure from stockholders, Jerica Pitts, Pfizer’s director of global media relations, said the company was not required to release the report but it had always planned to do so at its discretion.
“We had always said that we would share interim results given how needed this breakthrough could be,” Pitts stated in an email to National Geographic. “We have shared that these [results] are not conclusive and only observe those participants who have not previously been infected or contracted COVID-19.”
In their press release, the companies said the next step was to collect more safety data and apply to the FDA for an emergency use authorization in the third week of November. The agency requires that a vaccine-maker provide two months’ worth of safety data for at least half its phase three participants before such an authorization will be considered.
Yet recent meetings of vaccine advisory committees at the FDA and CDCindicated that regulators were considering the idea of swapping an emergency authorization with what’s known as an “expanded access,” or “compassionate use” license.
Such a step would limit how many people could receive a frontrunner vaccine, which would come with pros and cons. It would still allow access for dire situations, such as for frontline health-care workers and vulnerable communities, but there’d be reduced access for the general public. By contrast, an emergency authorization would mean no one could be denied the vaccine, which would essentially eliminate the ability to complete clinical trials for a vaccine candidate. People in placebo groups could request the vaccine, and scientists could no longer judge in a systematic way if the drug was truly working or safe.
Offit says a change in licensing goals might also be a positive step in encouraging more public confidence, given that some previous emergency use decisions, such as the one for the antimalarial drug hydroxychloroquine, have been controversial. “It’s better language,” says Offit, explaining that some emergency authorizations have been seen as being politically motivated on inadequately tested treatments. “I don’t think people should be suspicious of this vaccine.”
Some experts questioned why the companies chose to issue a press release before the safety data were ready. “There was no need,” says Doshi. “We could have waited two weeks for more complete data.”
But Wachter counters that any concerns about patient safety probably would have surfaced by now. “It would be nice to have more information on symptoms and how many were hospitalized. But the data is good enough so that I’m not worried about people over-interpreting the results,” he says. He adds that the data monitoring committees will stop a trial for suspicious or significant side effects. So far, that’s happened for three other COVID-19 vaccine trials, but not with Pfizer’s.
In fact, Wachter suggests the companies had a moral obligation to release early good news during this particularly grim phase of the pandemic. The announcement's influence on people's perceptions of the vaccine and the stock market isn't problematic as long as the interim report is truthful and suitably caveated, he says.
“This is incredibly promising news, and it seems quite unlikely that more detailed results will lead to a different conclusion than we're seeing now,” he says. “You could wait until they cross every last t. Then there’s another argument that it’s unethical to sit on the data any longer than you need to.”
Coronavirus: how the Pfizer Covid-19 vaccine works
The jab uses lab-created genetic material to produce a life-saving immune response
The experimental vaccine leading the race to provide coronavirus immunity depends on an entirely new approach to preventative medicine.
Indeed, if such a vaccine “was approved for coronavirus, it would be the first of its type” to deliver a successful immunisation, research magazine Horizon reported back in April.
Although the breakthrough injection - developed by the US drug company Pfizer and German research lab BioNTech - has not yet been approved, it has been shown to be 90% effective in protecting people from Covid-19.
How does it work?
Most vaccines rely on weakened or inactivated parts of the virus to provoke an immune response in their recipients, but the Pfizer version is synthetic.
The new vaccine - which is still undergoing Phase 3 trials - is made using messenger ribonucleic acid (also known as messenger RNA or mRNA). Whereas DNA is where we store our genetic information, mRNA - as its name suggests - transmits information and helps to determine how our genes are expressed.
To put that another way, mRNA “essentially puts DNA instructions into action”, says Horizon.
In the case of the Pfizer vaccine, the researchers synthesised a form of mRNA that will “cause our own cells to make a viral protein” from the Covid-19 coronavirus, says The New York Times.
The protein is harmless in isolation, but prompts the human immune system to “make antibodies and immune cells that can recognise the protein quickly and deliver a swift attack”, the newspaper adds.
Since the active ingredient in the vaccine - the mRNA - is “made from a DNA template in a lab”, says Pfizer, scaling up production is “a more rapid process than [with] conventional vaccines and a major advantage when it comes to sudden pandemics”.
Russia says coronavirus vaccine 92 percent effective
Russia's sovereign wealth fund said Wednesday that interim trial results indicated that the country's Sputnik V vaccine is 92 percent effective at protecting against COVID-19. Russia registered the vaccine candidate for public use in August, making it the first vaccine in the world to receive such approval. But the large-scale trial didn't start until September. The initial results came days after Pfizer and BioNTech reported that their vaccine candidate was more than 90 percent effective in its trials. Russia's interim results were based on data from the first 16,000 participants to receive both required doses of the vaccine. "We are showing, based on the data, that we have a very effective vaccine," said Kirill Dmitriev, head of the Russian Direct Investment Fund, which is backing and marketing the vaccine.
Persistent Virus Immunity: Potentially Good News on the Horizon for All Three Leading Candidate Vaccines
According to new research, immunity to the coronavirus may last years, perhaps even decades.
That’s good news because some experts worried that resistance to the virus could be fleeting, and it’s potentially great news for our ability to keep the virus under control with vaccines.
For months, reports of waning antibody levels led scientists to fear that resistance to the virus may be short lived. But researchers from the La Jolla Institute for Immunology who led the study looked at the body’s immune response in 185 patients, ages 19 to 81, who had recovered from the virus.
They tracked antibodies, but also B cells that can make more antibodies, and two types of T cells that kill other infected cells. The researchers also took blood samples from 38 people over many months.
The team found that antibodies stuck around, declining modestly six to eight months after infection, although the amount varied widely among the participants. T cells showed only a slight, slow decay in the body, while B cells actually grew in number. Researchers extrapolated from the slow level of decline over eight months, and concluded that people would most likely be protected for a few years. (How long, exactly, is still hard to predict.)
This is really good news. Because if natural infection is producing such a strong immune response, a vaccine certainly will, because vaccines generally tend to produce stronger, more durable immune responses than natural infections.
Experts also initially worried that resistance to the coronavirus might be similar to the flu, which would require people to be vaccinated every year. That would have created a logistical nightmare: The entire world would have to be vaccinated regularly just to keep the pandemic under control. But this research implies that may not be the case.
It suggests we may have some breathing room, and that may help every country get back on its feet, in terms of the economy and keeping its population safe.