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Tuesday, December 6, 2022
Dr. Brown: COVID could lead to generic vaccines for future

After more than a year of turmoil, suffering and death, there’s been one shining light in this pandemic – the rapid design of several highly effective vaccines.

Troubles associated with the rollout of the vaccines have been another matter, what with manufacturing challenges, shortages and the unwillingness of many to take the vaccine, thus imperilling hope of achieving herd immunity.

But there’s a race going on with this virus – can we vaccinate enough people worldwide quickly enough to prevent the emergence of variants that outwit the present vaccines?

All viruses undergo mutations and, as viruses go, this one mutates relatively slowly. Most mutations are neutral: they don’t affect the ease with which the virus spreads or the severity of the infection.

But when, as in this case, the virus finds so many hosts around the world, sooner or later some of those mutations will prove to be dangerous because they make it easier for the virus to spread, make the virus more lethal or help the virus to escape naturally or vaccine acquired immunity or combinations of those three options.

That’s precisely what’s happened with this virus. Within a few months, several variants appeared that proved to be highly transmissible. In the cases of the U.K., South African and Brazilian variants, they were more virulent. The appearance of the U.K. variant in particular was probably the reason for the rapid spike in cases initially in the U.K. and soon thereafter in Europe, the U.S., Canada and now India.

Most variants involve a combination of two or more mutations, which affect the virus’ spike proteins and hence the ease with which the spikes lock onto the host cell’s ACE-2 receptors and open the cell’s interior to the virus.

Once there, the virus RNA highjacks the cell’s machinery to make thousands of copies of the virus, before finally bursting the cell and releasing those copies into the circulation.

So far, the mutations and variants have failed to significantly reduce the clinical effectiveness of the current crop of vaccines – that is, the risk of hospitalization or a serious case of COVID. But clearly that’s possible in the future and the reason why manufacturers and public health laboratories monitor the changing genomic face of this virus looking for novel, potentially much more dangerous mutations and variants, and possibly incorporate modifications to their vaccines to maintain their effectiveness.

That’s one way to go about solving the problem of variants. Other scientists early on in this pandemic suggested another path: Why not develop vaccines that target well-conserved regions of the virus’ genome, which are far less susceptible to mutations?

And going much further, why not develop vaccines against all coronaviruses that have targeted humans such as SARS-CoV-2 (the current COVID-19 virus), SARS-CoV (the original SARS), MERS-CoV and others known to cause the common cold? Why not, indeed.

That approach that was suggested to the National Institute of Allergy and Infectious Diseases (NIAID) early on in this pandemic, a proposal that reviewers considered an “outstanding” idea, just not then when most vaccine developers wanted to urgently develop vaccines for this specific virus, never imagining the virus would become the menace it became and continues to be.

But now that vaccine developers have the upper hand, it’s time to return to a more generic proposal designed to deal with future variants by combining into one vaccine highly conserved, unlikely to change, antigenic components from all coronaviruses that attack humans.

Catching up with variants on the fly by modifying current vaccines as new variants erupt is expensive and probably not a viable solution for what has become a worldwide problem that’s going to be with us for the foreseeable future.

A generic vaccine would make a marvellous booster vaccine once the pandemic settles down, as a barrier to future budding pandemics. As it turns out, many scientists involved with designing flu vaccines are looking at a similar approach – combine antigenic components from as many flu variants as possible into one vaccine.

For both the coronavirus and influenza virus, the idea is to attach those representative antigenic protein components to some form of nanoparticle lattice – so constructed – that every antigenic protein has an equal opportunity to stimulate the immune system. It’s a clever idea that perhaps has found its time.

A similar solution for two families of viruses makes sense to me. And none of us will miss the common cold should such a generic coronavirus vaccine turn out to work. Indeed, has anyone had a cold or flu this season? So far, it’s been a “no flu” season.

That's a blessing in the carnage of COVID-19.

Dr. William Brown is a professor of neurology at McMaster University and co-founder of the Infohealth series at the Niagara-on-the-Lake Public Library.