It was the fastest vaccine development in history. But now pharmaceutical companies are getting ready 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, more deadly or more resistant to vaccines, pharmaceutical companies that responded in record time are racing to avoid new threats.
Scientists are confident that they can respond. The question is, how quickly?
Moderna – which together with rivals such as BioNTech / Pfizer and the partnership with the University of Oxford / AstraZeneca developed their vaccines in less than 12 months – announced on Monday that it would begin human testing of a new reinforcement adapted to reach the strain first 501.v2 identified in South Africa.
“We just want to be super cautious because this virus is complicated, as we all learned the hard way last year,” Stéphane Bancel, chief executive of Moderna, told the Financial Times. “We cannot not move now. . . because it would take months to get the next one ready if we needed it. “
Moderna decided to start a new trial after discovering that its vaccine produced antibody levels six times lower for 501.v2 than for other strains already identified.
One reason for the rush is that the more widespread 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 widespread variants, including B.1.1.7 which was responsible for a sharp increase in cases in the UK and the 501.v2 variant, no vaccine producer has published data on the worrying P.1 variant found in Brazil.
The data so far suggest that existing vaccines are effective against some of the most widespread variants © Joseph Prezioso / AFP / Getty
For pharmaceutical companies, saving time whenever possible from initial development, testing and manufacturing will be crucial if existing vaccines stop working against emerging strains.
“The vaccines used today are all based on the original Wuhan [viral DNA] If there is an impact on vaccines, it is likely to be widespread, ”said Dan Barouch, a Harvard researcher who helped design the Johnson & Johnson vaccine candidate.
It is not the underlying technology of how the vaccine is made, he added. “It’s about when you pull the trigger to decide whether to get a new vaccine.”
Preparing prototype vaccines and boosters
In preparation for the worst, scientists have been working on experimental vaccines that can work against recent variants, such as 501.v2 and P.1.
“As soon as these variants became apparent, we started to work on vaccines that aimed [them]”Said Mene Pangalos, executive vice president of biopharmaceutical R&D at AstraZeneca.
He said it would take one to three months for the prototypes to be ready and that the goal was to have a candidate who targeted “all major variants in circulation”. Then, the company would start clinical trials.
Nathalie Landry, executive vice president for 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 all vaccine manufacturers to do the same.”
Ms. Landry said it takes about 20 days to insert and cultivate the genetic sequence for the new variant in a plant culture, so that it forms virus-like particles. This then leads the immune system to think that it is encountering a viral particle.
Teams that produce other types of vaccines said the process of making a new vaccine prototype would take just a few days.
She pointed to the annual flu vaccine, which is adjusted every year depending on the most virulent strains in circulation. As there are usually several different strains, vaccine manufacturers produce four separate vaccines to give in a single injection.
Preparing prototypes of vaccines and boosters will now allow companies to move quickly towards small-scale testing when new strains of the virus emerge.
With Sars-Cov-2, Ms. Landry explained that if the World Health Organization or regulators determined that a previous strain was no longer in circulation, “we would rotate the manufacturing completely”, but “if the recommendation is that we will need to add another strain, we would have to divide our production in two ”.
Existing technology can be used
Bancel said that Moderna stopped seeing the virus sequence to send the first doses of its experimental vaccine in 42 days, but that “we could probably be faster in a new version, if necessary”.
He told FT that changing manufacturing would be “very easy” because almost everything in the formulation of the drug would remain the same. The only difference is the genetic sequence, made of “plasmid”, a small circular piece of DNA. Moderna plans to produce new plasmids for the 501.v2 variant and store this ingredient if necessary.
Stéphane Bancel, chief executive of Moderna, said changing manufacturing would be “very easy” © Adam Glanzman / Bloomberg
Germany’s BioNTech, which, like Moderna, produced a new type of vaccine based on messenger RNA, said it could use existing technology to quickly produce a new vaccine against virus mutations.
“The beauty of mRNA technology is that we can start to directly develop a vaccine that completely mimics this new mutation and we can manufacture a new vaccine in six weeks,” said Ugur Sahin, chief executive of BioNTech, last month.
Mr. Pangalos, from AstraZeneca, also admitted that mRNA vaccines “probably have a 4-6 week lead”.
Umesh Shaligram, director of research and development at the Serum Institute of India, the world’s largest vaccine manufacturer, said that “remaking the vaccine will not take long”.
In partnership with five international pharmaceutical groups, including AstraZeneca and Novavax, the Serum Institute has pledged to produce 1 billion doses of vaccine in 2021.
Dr. Shaligram said the company has the technology to replace the vaccine’s crucial ingredient without changing any of the other components. However, he admitted that it could take six months to increase production capacity.
‘Transition studies’ may be the key
Discussions with regulators have resulted in vague commitments that packaged studies will be accepted as evidence of the safety and efficacy of new vaccine formulations. But there is still debate about what exactly these tests would involve.
The UK Medicines and Health Products Regulatory Agency said “transition studies” would probably be needed – to gather existing data on quality, safety and efficacy and information on the modified product. He said he would try to conduct them in “the shortest possible time”.
Bancel, from Moderna, pointed out that seasonal transition 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.
Pangalos said that if the studies needed only to demonstrate a robust immune response, they would likely require only 1,000 patients. For AstraZeneca, these tests can take up to three months, he added. “We would get the data by the end of the year in time for next winter, that would be the goal.”
For Covid-19 vaccines that have already been authorized, the U.S. Food and Drug Administration required an average of two-month follow-up data to monitor safety, which extended the time needed to place them on the market.
But Andrey Zarur, chief executive of GreenLight Biosciences, which is developing a Covid-19 mRNA vaccine, said the FDA had informed the company that it would not need to retake safety tests if all the ingredients in the vaccine were the same and only the sequence viral has been changed.
“We have guarantees from the FDA that if we continue with a DNA strain and then change it, we will not need to start with clinical trials at an early stage,” he said.
The FDA said it had “thought about developing a potential path” for changes in Covid-19 vaccines and treatments.
Search for a Holy Grail vaccine
Several large laboratories are analyzing how the virus mutates in the face of threats, in an attempt to anticipate the likely variants.
Others are busy researching a Holy Grail vaccine that works against all coronaviruses, not just Sars-Cov-2.
Vir Biotechnology, an infectious disease company based in San Francisco, is working 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, chief executive of Vir Biotechnology.
Barney Graham, deputy director of the Vaccine Research Center at the US National Institute of Health, said a universal vaccine was the ultimate goal, and he has been working since 2017. But there was little time for this type of research during a pandemic.
Jesse Goodman, a former FDA chief scientist and professor at Georgetown University, believes that governments and regulators should work hard for this vaccine and that studies of promising candidates should begin immediately.
“I don’t think it’s a question of one day getting a different strain of coronavirus that has significant potential to escape the vaccine’s immunity, but when,” he said. “You don’t want to wait until it really happens to decide what you can do.”
Additional reporting by Stephanie Findlay