The technology exists to rapidly tweak vaccines in the face of new coronavirus mutations. But it would take time, and a global strategy is needed to ensure that scientists stay one step ahead.
The emergence of more transmissible variants of Sars-CoV-2 has prompted debate over whether the vaccines developed to date will continue to give protection. Although there is little evidence to suggest this is an issue with the variants detected in the UK, South Africa and Brazil, immunologists fear further mutations.
“The virus itself doesn’t have a particularly fast rate of mutation, but there is so much transmission and so many cases all around the world that the virus is being placed under this huge pressure,” said Katrina Pollock, a professor of vaccinology at Imperial College London.
Sharon Peacock, executive director and chair of the Covid-19 Genomics UK (Cog-UK) consortium, set up to sequence the virus, said: “Once you start to introduce a vaccine, there’s [further] selective pressure on the virus to try to find a way to get around it and persist, because that’s what evolution’s all about. It is possible that new vaccines will be required.”
The production of a new influenza vaccine each year shows it is possible to tweak vaccines to keep up with viral mutations. To do this, sentinel labs around the world are constantly sequencing the genomes of flu viruses gathered from patient samples and exposing these viruses to antibodies from people who have been vaccinated. This allows them to identify which strains are making people ill, the extent to which they are spreading, and how well the previous season’s vaccine protects against them.
Twice a year, the World Health Organization (WHO) coordinates a meeting of regional experts who use this data to decide on the next influenza vaccine.
In the case of flu, the vaccine is made by growing the chosen virus strains in fertilised eggs, inactivating it, and then packaging proteins from four different flu strains into a single vaccine. “All of that takes a long time and a lot of eggs, and it’s pretty labour-intensive,” said Peter Openshaw, a past president of the British Society for Immunology and a professor of experimental medicine at Imperial College London. “But it is a well-practised machine that swings into gear in order to supply a vaccine that is different each year.”
Newer technologies such as RNA vaccines could make this even easier, because they do not involve growing any virus. Instead, RNA vaccines contain a small piece of genetic code that provides our own cells with the instructions to manufacture the viral spike protein that triggers an immune response. “You can just dial in the genetic coordinates and reprogram the synthesis to make a new strand of RNA which is matched to the most commonly circulating strains,” said Openshaw. “Within six weeks of making a decision, [manufacturers] could produce a new tested batch of RNA vaccine.”
It is unlikely that regulators would require large-scale clinical trials to approve minor tweaks to vaccines, although smaller studies would be needed to ensure they were safe and triggered a similar antibody response.
Even so, global agreement may be needed. “The scientific side of it is straightforward; it would be the regulatory side that might be more of a challenge,” said Dr John McCauley, director of the Worldwide Influenza Centre at London’s Francis Crick Institute, one of six centres around the world that analyse influenza samples to help guide vaccine development.
“If a vaccine is going to be produced globally, then you need a global recommendation on its composition. For flu, that’s worked out through the WHO making a recommendation and regulators in different countries fine-tuning them. It requires cooperation and a recognition by the regulators that they are not necessarily in the best position to make a decision.”
Whether this would also hold true for Sars-CoV-2 is unclear. “Countries’ regulators understand the importance of having a global strategy for flu. I hope that the same will be the case for Sars-CoV-2, since the virus spreads as fast as flu,” said McCauley.
One solution may be to piggyback on the surveillance and decision-making framework developed for influenza. Doing so would require the expansion of viral genome sequencing by labs in different countries, plus the gathering of data on how long vaccines protect for and how well they work against emerging variants, not to mention international sharing of this data.
“It is going to be something of a cat-and-mouse game, but I feel confident that through a combination of sequencing, surveillance and [working with] vaccine manufacturers, we can stay ahead of the curve,” Peacock said.