TOPICS: COVID-19

News that the novel coronavirus is mutating has prompted debate over whether existing COVID-19 vaccines will continue to protect against new variants. There is little evidence to suggest that current SARS-CoV-2 variants, including the British and South African variants, could escape the immune protection afforded by those vaccines authorised for emergency use or in development. But many immunologists are concerned about the possibility of them accruing further mutations, which could render these vaccines less effective in the future. Others have pointed out that such vaccines could be “tweaked” to overcome this problem. But what does this involve, and how easy is it to achieve?

The production of a new influenza vaccine each year demonstrates that it is possible to adapt existing vaccines to keep up with viral mutations.

Keeping up with flu and meningitis

The idea of altering existing vaccines to cover additional or emerging variants isn’t a new one. Each year, a new influenza vaccine is developed and delivered to clinics around the world to reduce the number of flu-related hospitalisations and deaths. The influenza virus mutates more rapidly than coronavirus, so sentinel sites around the world are constantly sampling and sequencing the genomes of virus samples from patients to identify which influenza viruses are making people ill, and the extent to which those viruses are spreading.

Clinical studies also measure how well the previous season’s vaccine protects against these emerging viruses. Then, twice a year, the World Health Organization (WHO) coordinates a meeting of regional experts who decide which viruses to include in that year’s influenza vaccine.

The flu jab is an inactivated whole virus vaccine, meaning it contains influenza viruses whose genetic material has been destroyed so they cannot infect cells and replicate, but they can still trigger an immune response. Creating a new flu vaccine therefore involves isolating samples of the chosen viruses and then growing them in chicken eggs, before inactivating and purifying them, and then packaging them into individual vaccine doses.

Other types of vaccine are also tweaked to keep up with changing global health needs. For instance, pneumococcal conjugate vaccines, which protect against disease caused by Streptococcus pneumoniae bacterium – including pneumonia, meningitis and sepsis – is a subunit vaccine, which uses purified fragments of bacteria attached to carrier proteins to trigger an immune response.

The first pneumococcal conjugate vaccine, called PCV7, contained a cocktail of fragments from the seven most common strains of S. pneumoniae; but later vaccines, such as the Pneumococcal Conjugate Vaccine 13, contain fragments from additional strains (in this case, 13 out of 92 existing strains). This is because once circulation of the original seven strains was reduced as a result of vaccination, some of the other strains that had previously been competing against them began causing more disease.

Tweaking a subunit vaccine involves identifying antigens capable of stimulating a strong immune response from the additional strains of viruses or bacteria you wish to vaccinate against, and then inserting the genetic code for all of these antigens into yeast or bacterial cells that are grown in large fermentation tanks or bioreactors.

It should also be relatively straightforward to deliver an updated version of any COVID-19 vaccine into existing supply chains.

NEW TECHNOLOGIES

What about RNA vaccines, like the Moderna and Pfizer/BioNTech vaccines, or viral vector vaccines, such as the one developed by Oxford University/AstraZeneca? In theory, it should be possible to tweak these vaccines to keep up with mutating coronavirus variants – although the method would differ for each.

RNA vaccines are made by synthesising strands of RNA from a DNA template, and then packaging it into fatty capsules that make it easier to get the RNA into our cells. Tweaking the vaccine would mean adjusting the code of the DNA template, which should be a relatively quick and simple process – although this has no historical precedent, because the current COVID-19 vaccines are the first such RNA vaccines to receive authorisation. Possibly, different stands of RNA could be combined in a single vaccine to cover the current strain of coronavirus, as well as future ones – although this also has never been tested.

Modifying an existing viral vector vaccine is also unprecedented, but theoretically possible. The AstraZeneca/Oxford vaccine contains a common cold virus called an adenovirus, which has been adapted to carry a piece of genetic code for the coronavirus spike protein, and disabled so that it cannot cause disease.

Tweaking this sort of vaccine would probably involve modifying the vaccine adenovirus so it contains a slightly different piece of code matching the spike protein from the new coronavirus variant(s), and then culturing large amounts of this virus by growing it in cells. One potential obstacle is that of anti-vector immunity, wherein the immune system might recognise the adenovirus used to deliver the spike protein code from the original round of COVID-19 vaccination and attack it, thereby reducing the effectiveness of the vaccine. This might necessitate the development of additional viral vectors for subsequent vaccinations.

STAMP OF APPROVAL

The production of a new influenza vaccine each year demonstrates that it is possible to adapt existing vaccines to keep up with viral mutations.

Regulators do not require evidence from large-scale clinical trials to approve such vaccines, but smaller studies are necessary to ensure that the modified antigen triggers a similar antibody response to the original vaccine – which would imply that the new vaccine provides a similar protection against the virus.

It should be relatively straightforward to deliver an updated version of any COVID-19 vaccine into existing supply chains – although factors such as the price and effectiveness of the updated vaccine, relative to the original, might influence its uptake in different countries.

In summary, it should be possible to tweak existing COVID-19 vaccines, should new variants emerge that escape the immunity they confer – although this remains a theoretical challenge for the time being. Even so, international surveillance to identify emerging variants and track their spread will be essential to ensure we stay a step ahead of COVID-19. Studies must also monitor how long the protection afforded by existing vaccines lasts and whether they will continue to protect against any new variants that emerge.

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