There's no guarantee a coronavirus vaccine will last a lifetime – antibodies are only part of the story

Two important studies on the human immune response to a Covid-19 infection are causing scientists to reassess how vaccines might work and be delivered.

Hopes remain that a “one-shot-and-you’re-protected-for-life” vaccine will still emerge, but the more we learn about the immune response to the virus, the less straightforward that seems. 

It is more plausible, say some experts, that the first Covid vaccines will be time-limited, requiring booster shots every few years. Others may work, not by preventing infections completely, but by relieving the worst of the symptoms.  

The first of these new studies shows that the protective antibodies fade relatively quickly from the blood – just as they do with other coronaviruses.

Of 96 people tracked by a team at King's College London, 60 per cent had a “potent” Covid-19 antibody response at the height of their infection. But this fell to just 17 per cent three months later – in some, antibodies were almost undetectable. 

The second big finding is more positive and relates to T cells, white blood cells that help the immune system fight off viruses. Several studies have detected T cell reactivity against Sars-CoV-2 in those who have never been exposed to the virus.

“It is speculated that this reflects T cell memory to circulating ‘common cold’ coronaviruses,” says a recent review in the journal Nature. “It will be important to define specificities of these T cells and assess their association with Covid-19 disease severity and vaccine responses.”

So what are the implications for vaccines development? Does the fact that natural antibodies fade quickly mean that the efficacy of vaccines will be equally short-lived? And what are the repercussions of the T cell response? 

For the moment, vaccine specialists remain calm. They point out that fading antibodies does not necessarily equate to fading immunity – it is entirely possible that antibodies in our blood may fall below detectable levels while still providing an effective defence against reinfection. 

Similarly, the type of immune response triggered by a vaccine is not necessarily the same as that which follows a ‘natural’ infection. Some vaccinations produce a stronger and longer-lasting protection than the disease itself, including the tetanus and HPV jabs.

“A virus may dodge the [natural] immune system if it can to avoid being detected but that is not the case for all vaccines, which are often engineered solely to raise immunity,” says Ian Jones, a professor of virology at the University of Reading.

Nevertheless, fading antibodies may pose a stumbling block for some candidates. In particular, vaccines which use an attenuated or dead version of the actual Sars-Cov-2 virus to prompt an immune response may be rendered less effective.

“Those vaccines might be less attractive based on these studies because if the real viral infection doesn't give you a long and powerful immune response, you might expect that by weakening the virus you have an even lower immune response,” says Dr Al Edwards, from the University of Reading’s school of pharmacy.

Of the estimated 224 vaccines in development, at least 17 fall into this category. They may work but they may also require regular booster-shots to keep them performing.

T-cells add to the complexity. “If you were analysing a country’s defence system, you wouldn’t just look at the army and ignore the navy,” says Dr Edwards. “It’s similar here – antibodies are only part of the story.”

The British vaccine research teams at Imperial and Oxford hope their high-tech RNA and adenovirus based vaccines have both T-cells and the problem of fading antibodies covered.

Prof Sarah Gilbert, leader of the Oxford project, says there is a good chance this vaccine will prompt a strong and lasting response in both.

“This is something that we will need to assess in vaccine trial participants as time goes on, but in other trials of [similar] ChAdOx1-vectored vaccines, responses have been well maintained a year after vaccination,” she says.

But even these vaccines may not reach the gold ‘one shot’ standard. Early data from the Oxford study, for example, suggest the virus may not provide complete protection – perhaps only warding off Covid-19’s worst symptoms. 

“Ideally we’d like immunity from a vaccine to completely wipe out a virus,” says Dr Andrew Preston of the University of Bath. “But if we can reduce Covid-19 to a seasonal cold, that would be good enough compared to the current alternative.”

“[The latest research suggests] there is no guarantee that a vaccine will be found that confers lasting immunity,” adds Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine. “It’s possible immunity will be short-lived or even non-existent. We await the results of the trials.”

There are three other bits of emerging Covid science that vaccine teams are keeping a close eye on – two encouraging and one a bit terrifying.

On the bright side, the virus itself seems stable with no major mutations yet recorded which would derail vaccine development. And the focus of nearly all vaccine teams on disrupting the virus’s ‘spike protein’ looks correct, with more and more research showing its importance. 

On the dark side, there is a “nagging concern” that the worst cases of Covid-19 could actually be linked to T-cells generated by the common cold, adds Dr Edwards.

A review in Nature described this as the risk of ‘original antigenic sin’, where the presence of T cells triggers an inferior immune response that actually makes the disease worse. 

“There’s no indication that this is the case, but it’s just possible that some vaccine candidates will trigger an immune response that makes the virus more severe”, said Dr Edwards. “You just need to look at dengue fever… there are four types, and you almost always have a more severe disease after the second infection”. 

Let’s hope Covid does not take after dengue.

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