In April, Sarah Gilbert, the British scientist leading Oxfords COVID-19 vaccine effort, said she was 80 percent confident her team would be able to produce a successful vaccine by September.

It was a remarkable statement — conspicuously confident — especially given the timing: Oxfords vaccine had yet to be tested in a single human, and the results from a preliminary trial involving monkeys hadnt yet been published.

With pandemic death rates in the U.S. and Britain ratcheting upward, Gilberts forecast soothed panicky citizens who had been told that it typically takes years to develop a successful vaccine. The New York Times wrote that Oxford had leapt ahead of the competition and was “sprinting fastest” to the finish line. Within weeks, Oxford had partnered with British pharmaceutical giant AstraZeneca and the two were inking deals around the world to manufacture and distribute hundreds of millions of doses. The vaccine became one of the worlds best hopes: By late August, with Phase III trials to determine safety and efficacy ongoing, the world had ordered more of the Oxford candidate than any other, at least 2.94 billion doses.

Now, Gilberts and the worlds hopes are coming back down to earth, with the news that AstraZeneca paused Phase III trials after one participant in Britain showed symptoms consistent with transverse myelitis, a rare neurological disease caused by inflammation of the spinal cord. Obstacles like this one are not unexpected in vaccine development, say experts. The fact that AstraZeneca is pausing trials to investigate, they point out, is a good thing — a signal that that system is working as it should, that drug companies are taking safety seriously, that there are some scientific norms that politics hasnt trampled.

But the interruption is also a reminder that no amount of hype — from the endless media headlines, from politicians on Twitter, from the vaccine scientists themselves — is going to save the world from the deadliest pathogen in a century. This weeks news is a cautionary note for those who think a magic bullet might be around the corner — or who think that it might be worth slashing safety protocols to get one.

In fact, the Oxford/AstraZeneca groups self-assurance raised some eyebrows right from the start.

“I felt this way about a number of the companies,” says Paul Offit, director of the Vaccine Education Center at Childrens Hospital of Philadelphia and co-creator of a rotavirus vaccine. “They would do small Phase I trials, basically dose-ranging trials, and then talk about how they could make tens of millions of doses.”

“How about a little humility?” he thought.

Gilberts prediction reflected more “pride than reality,” says Michael Kinch, director of the Centers for Research Innovation in Biotechnology and Drug Discovery at Washington University in St. Louis. “The reality is that developing a vaccine … is generally quite challenging. Oftentimes, you dont see the big problems coming.”

This week, that reality arrived for the Oxford vaccine. An independent committee must now determine whether the illness is directly linked to the vaccine or not — both possible outcomes. If the two are related, that will likely be the end of this vaccine. If not, the trial will likely resume after several weeks.

The hitch is also a reminder that a lot of COVID-19 science is uncharted territory. “We dont have much experience with these types of vaccines,” says Tom Frieden, former director of the Centers for Disease Control. Adenovirus vectored vaccines, like Oxfords, are relatively new, and mRNA vaccines — like those developed by Moderna and Pfizer — have never been used before in humans. The Trump administration is reportedly making plans to distribute the Moderna and Pfizer candidates, which are still in Phase III trials, in the U.S. by early November.

Kinch is worried that many countries are placing big bets on these newer vaccine technologies, while shunning old, established ones like inactivated virus vaccines, which China is pursuing. Thats one more reason to take safety with COVID-19 vaccines very, very seriously.

“Well designed and executed studies are so crucial,” he wrote in an email. “Autoimmune sensitives can be rare … and often take time (weeks or months) to develop.” Which means rushing a trial can be deadly. “A one in a thousand [reaction] sounds rare except when you scale those numbers up to 350 million Americans, or seven billion humans worldwide, the outcomes can be disastrous.”

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Oxford was at the front of the pack from day one.

A few years ago, Gilbert, a top scientist at the universitys Jenner Institute, created a MERS vaccine by inserting genetic material of the MERS surface spike protein into a weakened chimpanzee adenovirus (a common cold virus). Once in the body, the adenovirus infects cells and unloads the gene, hopefully generating an immune response. The vaccine started trials in December in Saudi Arabia, where MERS is still a concern.

A month later, in January, when Gilbert heard about a mysterious, deadly pathogen raging through Wuhan, she was ready: Her team simply inserted genetic material from the spike protein of the SARS-CoV-2 virus inside the chimp adenovirus instead, theorizing that would confer immunity to the new virus.

“The MERS study was absolutely critical,” one of Gilberts vaccine colleagues told Bloomberg. “We could say, OK, we can start tomorrow.”

In the first test of the vaccine, scientists inoculated six monkeys before exposing them to a large dose of SARS-CoV-2. Adrian Hill, Gilberts colleague who leads the Jenner Institute, called the results “fantastic” — none of the vaccinated monkeys showed signs of sickness after being exposed. In April, around the time the monkey results came in, the Jenner team began planning to mass produce their vaccine. “The aim is to have at least a million doses by about September,” Hill said at the time, describing that number as a “fairly modest target.” The Trump administrations Operation Warp Speed announced a billion-dollar investment in May.

The results of a combined Phase I/II trial in July reported no serious safety issues and showed that the vaccine produced neutralizing antibodies in those tested — an outcome that was deemed “encouraging” and “promising.” “This is very positive news. A huge well done to our brilliant, world-leading scientists & researchers at @UniofOxford,” tweeted British Prime Minister Boris Johnson before adding “there are no guarantees.”

But the vaccine had its skeptics, too. Nasal swabs showed the monkeys from the first test still had the virus in their nose, meaning they might still be able to spread the virus to others, and their neutralizing antibody count was quite low. In a Forbes article, former Harvard Medical School professor and prominent cancer and HIV researcher William Haseltine argued the Jenner Institute didnt have the data to support their claim that their vaccine protected the monkeys. “Time will tell if [proceeding to human trials] is the best approach,” he wrote. “I wouldnt bet on it.” The Phase I/II trial, meanwhile, reported levels of neutralizing antibodies comparable to those seen in recovered COVID-19 patients, but lower than those generated by other vaccine candidates. And the scientists administering the trial only tested 35 participants for antibodies out of 543 who had received the vaccine.

It was too early, scientists cautioned, to know whether this vaccine, or any other, was effective or safe. Incremental and early trial data might bump up stock prices, or even land a government contract, but it cant predict the future.

The final determination would only come at the end of large Phase III trials, which AstraZeneca began in the U.S. in late August. (The company began smaller Phase II/III trial in Britain, Brazil and South African in July.) Today, there are nine other vaccines currently in the Phase III stage — with no definitive results yet. “Lets be clear: No one knows anything” about the specifics of the vaccine timeline right now, says Zeke Emanuel, former Obama adviser and chair of the Department of Medical Ethics and Health Policy at the University of Pennsylvania. “Were all bullshitting.”

That doesnt mean that governments shouldnt be dealing for doses or investing in vaccine projects — that is no doubt why the COVID-19 vaccine process is unfolding historically fast. But scientists have worried that all the vaccine hype could push politicians to cut off the normal scientific process too soon. While Anthony Fauci and other top U.S. government health officials insist the U.S. will not rush science, President Donald Trump continues to agitate scientists with his rosy vaccine predictions, now a keystone of his election campaign, that the U.S. will have a vaccine ready by Election Day; just last month the Financial Times reported the Trump administration was considering fast-tracking approval of the Oxford vaccine if results from a 10,000-person late-stage clinical trial looked promising, rather than waiting until the 30,000-person Phase III U.S. trial was complete. (AstraZenenca said it had not discussed this with the Trump administration.)

But the news of AstraZenecas pause seems to have relaxed scientists a bit, confirming that drug companies are proceeding with caution and not neglecting safety even as theyre under pressure from governments to produce. It even soothed some early skeptics of the Oxford teams bravado.

“This is a hopeful sign that the organizatiRead More – Source

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