Covid vaccines: scientists seek ‘holy grail’ of long-term protection – Prof Eleanor Riley

Existing vaccines provide strong protection against severe Covid disease, but are not particularly good at preventing infection (Photo: Thibault Savary/AFP via Getty Images)

I doubt that anyone – expert or otherwise – could have predicted with certainty in March 2020 that a dozen different vaccines would be released by now, that more than 60 percent of the world’s population would be vaccinated, or that the pandemic would be defeated. (although perhaps temporarily) through vaccination in large parts of the globe.

But this, unfortunately, does not mean that we can say “job done” and move on. Our Covid vaccine challenge is just beginning.

Despite all their successes, our current crop of vaccines is not perfect. They provide very good protection against severe disease for all variants of the virus that we have encountered so far.

This kept most of the infected from reaching the hospital this winter and prevented hundreds of thousands of deaths. But even then, the effectiveness against severe diseases decreases over time, and periodic boosters are likely to be needed.

More worryingly, currently available vaccines are not particularly good at preventing infection, and that protection declines over months and is highly dependent on which variant is circulating. We cannot rely on the wide coverage of modern vaccines to stop the virus from circulating and, in the process, from mutating.

The Sars-CoV-2 virus is rapidly evolving to evade neutralizing antibodies, which are our first line of defense against infection. This is why fully vaccinated (and boosted) people test positive for Omicron and why we are seeing an increase in the number of people with a second or third infection.



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Fortunately, these “breakthrough” infections tend to be mild and often asymptomatic. However, they are a nuisance and a source of infection for other, more vulnerable people.

To limit virus transmission and mutation, we need vaccines that are much more effective at blocking infection, protect against a wide range of variants, and do so for long periods of time.

Blocking infection requires high concentrations of antibodies in the nose and throat. This can be helped by administering the vaccine intranasally or as an aerosol: the vaccine directly stimulates antibody-producing cells located in the lining of the nose and throat.

Protection against different variants can be achieved by continually updating the vaccine to reflect current circulating variants and/or combining multiple variants into one vaccine, as we do each year for influenza vaccines.

But a more effective way to deal with different variants is to develop a vaccine that targets the invariant or “conservative” parts of the virus; these vaccines induce broadly neutralizing antibodies that are effective no matter which variant you are exposed to.

This is the holy grail for influenza vaccine developers, and it is coming very close due to a more detailed understanding of the structure and function of viral proteins. Lessons learned are already being applied to Sars-CoV-2.

Increasing the lifespan of a vaccine is perhaps the biggest challenge. Immunity to cold coronaviruses is notoriously short-lived, which is why we often get reinfected. We must work better than Mother Nature. It is not yet clear whether mRNA or adenovirus vaccines can do this, but there are other approaches we can try. Alternatively, we may need regular boosters or occasional re-exposure to the virus to boost our immunity.

After all, this is what life with Covid might look like.

Eleanor Riley is Professor of Immunology in Infectious Diseases at the University of Edinburgh.

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