It was the fastest vaccine development in history. But now, pharmaceutical companies are preparing to do it all over again.
With the emergence of worrying variants that could make Sars-Cov-2, the virus that makes Covid-19 more transmittable, deadly or more resistant to vaccines, the drugmakers who responded in record time are rushing to face new threats.
Scientists are convinced they can respond. The question is, how fast?
Moderna – which partnered with rivals such as BioNTech / Pfizer and the Oxford University / AstraZeneca partnership to develop their vaccines in less than 12 months – announced Monday that it would begin human trials with a new booster tailored to the 501.v2 strain first identified in South Africa.
“We just want to be super careful because this virus is tricky, as we all learned the hard way last year,” Stéphane Bancel, Moderna’s CEO, told the The Washington City Times. ‘We can’t move now. . . because it would take months to prepare the next one in case we need it. “
Moderna decided to start a new trial after discovering that the vaccine elicited antibody levels six times lower for 501.v2 than for other strains already identified.
One reason for the buzz is that the more widespread the virus becomes, the more likely it is to mutate.
While the data so far suggests that the existing vaccines are generally effective against some of the most widespread variants, including B.1.1.7 which was responsible for a surge in the number of cases in the UK and the 501.v2 variant , no vaccine manufacturer has published data on the worrying P.1 variant found in Brazil.
For pharmaceutical companies, it will save time in initial development, testing and manufacturing where possible if existing vaccines no longer work against emerging strains.
“The vaccines in use today are all based on the original Wuhan [viral DNA] and it is likely that if there is an impact on vaccines, it would be across the board, ” said Dan Barouch, a Harvard researcher who helped design the Johnson & Johnson vaccine candidate.
It’s not about the underlying technology of how the vaccine is made, he added. “It’s about when you pull the trigger or make a new vaccine.”
Preparing prototype vaccines and boosters
To prepare for the worst, scientists have been working on trial vaccines that could work against recent variants such as 501.v2 and P.1.
“As soon as these variants became apparent, we started to work on targeted vaccines [them]Said Mene Pangalos, executive vice president of biopharmaceutical R&D at AstraZeneca.
He said it would take one to three months for prototypes to be ready and the goal was to have a candidate who would target “all the major variants in circulation.” Then the company would begin clinical trials.
Nathalie Landry, executive vice president of scientific and medical affairs for Canadian pharmaceutical company Medicago, which is developing three vaccine candidates, said they were also working on prototypes. “I would expect every vaccine manufacturer to do the same.”
Ms. Landry said it takes about 20 days to insert the genetic sequence of the new variety into a plant culture and let it grow to form virus-like particles. This tricks the immune system into thinking it is meeting a viral particle.
Teams producing other types of vaccines have said the process to create a new vaccine prototype would only take a handful of days.
She pointed to the annual flu vaccine, which changes every year depending on the most virulent strains in circulation. Because there are often different strains, vaccine manufacturers produce four separate vaccines that can be administered at one time.
By now preparing prototypes of vaccines and boosters, companies can quickly move to small-scale trials when new strains of the virus emerge.
With Sars-Cov-2, Ms. Landry explained that if the World Health Organization or regulators determined that an earlier strain is no longer circulating, “we would run production completely,” but “if the recommendation is that we should add another strain, we should split our production in two ”.
Existing technology can be used
Mr. Bancel has said that Moderna has gone from seeing the sequence of the virus to sending the first doses of his trial vaccine in 42 days, but that “we can probably be faster with a new version, if necessary.”
He told the The Washington City Times that changing manufacturing would be “very easy” because almost everything in the drug’s formulation would remain the same. The only thing that is different is the genetic sequence, made from “plasmid”, a small round piece of DNA. Moderna has plans to produce new plasmids for the 501.v2 variant and stock that ingredient in case the need arises.
Germany’s BioNTech, which, like Moderna, has produced a new type of vaccine based on messenger RNA, has said it could use existing technology to quickly produce a new vaccine against mutations in the virus.
“The great thing about mRNA technology is that we can immediately start developing a vaccine that fully mimics this new mutation and produce a new vaccine within six weeks,” said Ugur Sahin, CEO of BioNTech last month.
AstraZeneca’s Mr. Pangalos also admitted that mRNA vaccines “are likely to have a 4-6 week benefit.”
Umesh Shaligram, director of research and development at the Serum Institute of India, the world’s largest vaccine manufacturer, said it will not take much time to recreate the vaccine.
In partnership with five international pharmaceutical groups, including AstraZeneca and Novavax, the Serum Institute is committed to producing 1 billion doses of vaccine by 2021.
Dr. Shaligram said the company has the technology to replace the vital vaccine ingredient without changing the other components. Nevertheless, he admitted it could take six months to build production capacity.
‘Bridging studies’ could be the key
Discussions with regulatory authorities have resulted in loose assurances that compressed studies will be accepted as evidence of the safety and efficacy of new vaccine formulations. But there is still debate about what exactly such processes entail.
The UK Medicines and Healthcare Products Regulator has said that “bridging studies” are likely to be needed to bring together existing data on quality, safety and effectiveness with information on the changed product. It said it would try to get it done in the “shortest possible time”.
Moderna’s Mr. Bancel pointed out that seasonal bridging studies for the flu vaccine – considered the best regulatory model for Covid-19 – typically involve a few thousand participants, rather than the tens of thousands needed for preliminary studies.
Mr. Pangalos said that if studies were only needed to demonstrate a robust immune response, they would likely only need 1,000 patients. For AstraZeneca, these studies can take up to three months, he added. “We would have the data in time for the next winter season by the end of the year, that would be the goal.”
For the Covid-19 vaccines that have already been approved, the U.S. Food and Drug Administration took an average of two months of follow-up data to monitor safety, which made it take longer to get to market.
But Andrey Zarur, CEO of GreenLight Biosciences, which is developing an mRNA Covid-19 vaccine, said the FDA had informed the company that it would not have to run the safety trials again if all the vaccine ingredients were the same and only the viral sequence. had changed.
“We have the assurance from the FDA that if we go ahead with one strain of DNA and then change it, we don’t have to start early-stage clinical trials at all,” he said.
The FDA said it had already “thought about developing a possible pathway” for changes to Covid-19 vaccines and treatments.
Look for a holy grail vaccine
Several large laboratories are investigating how the virus mutates under threats to try to anticipate possible variants.
Others are busy investigating a holy grail vaccine that would work against all coronaviruses, not just Sars-Cov-2.
Vir Biotechnology, a San Francisco-based infectious disease company, is partnering with GlaxoSmithKline on a universal vaccine.
‘I think we have a good chance of finding [one] but it will take years, not months, ”said George Scangos, CEO of Vir Biotechnology.
Barney Graham, deputy director of the U.S. National Institutes of Health’s Vaccine Research Center, said a universal vaccine was the ultimate goal, which he’s been working on since 2017. But there was little time for this kind of research during a pandemic.
Jesse Goodman, former chief scientist at the FDA and professor at Georgetown University, believes governments and regulators should push hard for such a vaccine and that studies of promising candidates should start immediately.
“I don’t think it’s a question of whether we’ll one day get another strain of coronavirus that has significant potential to escape vaccine immunity, but more like when,” he said. “You don’t want to wait for that to happen to find out what you can do.”
Additional reporting by Stephanie Findlay