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 causes Covid-19, more transmissible, lethal or more resistant to vaccines, the drug manufacturers who responded in record time are chasing new threats.
Scientists are confident that they can respond. The question is: how fast?
Moderna – which has partnered with competitors such as BioNTech / Pfizer and the Oxford University / AstraZeneca partnership to develop their vaccines in less than 12 months – announced on Monday that it will launch human trials of a new booster tailored to the first 501.v2 strain to direct. identified in South Africa.
“We just want to be very careful because this virus is difficult, because we all learned the hard way last year,” Moderna CEO Stéphane Bancel told the Financial Times. “We can not move now. . . because it will take months to get the next one ready if we need it. ”
Moderna decided to embark on a new experiment after discovering that the vaccine elicited antibody levels for 501.v2 six times lower than for other strains already identified.
One reason for the rush is that the more spread the virus becomes, the more likely it is to mutate.
Although data to date suggest that existing vaccines are generally effective against some of the most common variants, including B.1.1.7 which was responsible for a sharp increase in cases in the UK and the variant 501.v2, no vaccine producer published. data on the worrying P.1 variant found in Brazil.
Data to date indicate that existing vaccines are effective against some of the most common variants © Joseph Prezioso / AFP / Getty
For pharmaceutical companies, it is crucial to save time from initial development, trials and manufacturing as existing vaccines no longer work against emerging strains.
‘The vaccines used today are all based on the original Wuhan [viral DNA] sequence and it is likely that there is an impact on vaccines, “designed Dan Barouch, a Harvard researcher who helped design Johnson & Johnson’s vaccine candidate.
It is not about the underlying technology of how the vaccine is made, he added. “It’s about when you pull the trigger or you make a new vaccine.”
Prepare prototype vaccines and enhancers
In preparation for the worst, scientists have been working on experimental vaccines that could work against recent variants such as 501.v2 and P.1.
‘Once these variants became clear, we started working on targeted vaccines [them]Said Mene Pangalos, executive vice president of biopharmaceutical research and development at AstraZeneca.
He said it would take one to three months for prototypes to be ready, and the aim was to have a candidate who would direct “all major variants in circulation”. Then the company will start clinical trials.
Nathalie Landry, executive vice president of scientific and medical affairs at 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.”
Landry said it takes about 20 days to insert the genetic sequence of the new variant into a plant culture and grow it to form virus-like particles. It misleads the immune system into thinking it encounters a viral particle.
Teams producing other types of vaccines said the process of making a new prototype for vaccines would only take a few days.
She points to the annual flu vaccine, which is adjusted each year depending on the most virulent strains in circulation. Since there are often different strains, vaccine manufacturers produce four separate vaccines to put in one shot.
With the preparation of prototypes of vaccines and boosts, companies can move quickly to small-scale trials when new virus strains emerge.
With Sars-Cov-2, Ms Landry explained that if the World Health Organization or regulators were to determine that a previous strain was no longer circulating, ‘we would turn production completely’, but ‘if the recommendation is that we still need some add, we will have to split our production in two ”.
Existing technology can be used
Mr. Bancel said Moderna had not seen the sequence of the virus after the first doses of his trial vaccine in 42 days, but that “we could probably go faster with a new version, if necessary”.
He told the FT that switching to manufacturing would be “very easy” because almost everything in the drug formulation would remain the same. The only thing different is the genetic sequence, made from ‘plasmid’, a small circular piece of DNA. Moderna plans to manufacture new plasmids for the 501.v2 variant and store the ingredient as needed.
Moderna CEO Stéphane Bancel said converting manufacturing would be ‘very easy’ © Adam Glanzman / Bloomberg
Germany’s BioNTech, which, like Moderna, has produced a new type of messenger RNA-based vaccine, said it could use existing technology to quickly produce a new vaccine against mutations of the virus.
“The beauty of mRNA technology is that we can start designing a vaccine directly that completely mimics this new mutation, and that we can produce a new vaccine within six weeks,” UN Sahin, CEO of BioNTech, said last month. said.
Mr. Pangalos of AstraZeneca also conceded that mRNA vaccines “probably 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 that “the reintroduction of the vaccine will not take much time”.
The Serum Institute has partnered with five international pharmaceutical groups, including AstraZeneca and Novavax, to deliver 1 billion vaccine doses by 2021.
Dr Shaligram said the company has the technology to replace the key ingredient of the vaccine without changing any of the other components. He nevertheless conceded that it could take six months to build up the manufacturing capacity.
‘Bridge studies’ can be the key
Discussions with regulators have led to loose commitments that compressed studies will be accepted as evidence of the safety and efficacy of new vaccine formulations. But there is still debate about exactly what such trials would entail.
The UK’s Medicines and Healthcare Regulatory Agency said it was likely to require ‘bridging studies’ – to gather existing data on quality, safety and efficacy and information on the modified product. It is said that it will seem to be done in the “shortest time possible”.
Moderna’s Mr Bancel pointed out that seasonal bridging studies for the flu vaccine – considered the best regulatory model for Covid-19 – usually involve a few thousand participants, rather than the tens of thousands required in preliminary studies.
Mr. Pangalos said that if studies are only needed to demonstrate a robust immune response, they probably only need up to 1,000 patients. For AstraZeneca, these trials could take up to three months, he added. “We will get the data by the end of the year in time for the next winter season, that is the goal.”
For the Covid-19 vaccines already approved, the U.S. Food and Drug Administration required an average of two months of follow-up data to monitor safety, which took longer to bring to market.
But Andrey Zarur, CEO of GreenLight Biosciences, which is developing a mRNA Covid-19 vaccine, said the FDA has informed the company that it is not necessary to perform safety tests if all the vaccine ingredients are the same and only the viral sequence is not. has been changed.
“We have the FDA’s assurance that if we continue with one strain of DNA and then change it, then we do not need to start clinical trials at an early stage at all,” he said.
The FDA said it had already considered a possible route to a change in Covid-19 vaccines and treatments.
Seek a vaccination against the holy grail
Several large laboratories are watching the virus mutate despite threats, trying to predict what is likely.
Others are researching a holy grail vaccine that can work against all coronaviruses, not just Sars-Cov-2.
For Biotechnology, a company in San Francisco that is contagious, is working with GlaxoSmithKline on a universal vaccine.
‘I think we have a good chance of finding it [one] but it will not take years, ”said George Scangos, CEO of Vir Biotechnology.
Barney Graham, deputy director of the Vaccine Research Center at the U.S. National Institutes of Health, said a universal vaccine is the ultimate goal, and one he has 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 insist strongly on such a vaccine and that studies of promising candidates should begin immediately.
“I do not think it is the question of whether we will one day find another coronavirus strain that has great potential to release the vaccine, but more like when,” he said. “You do not want to wait until that happens to find out what you can do.”
Additional reporting by Stephanie Findlay