Coronavirus: So Many Variants, But Vaccines Are Still Effective

31 May 2021

Viruses are constantly changing. This is because errors sometimes occur when they copy their genetic material. Some errors have no effect at all. Some might make the virus less viable. Some make it more benign, which means it can survive but doesn’t cause disease. The errors to watch for are those that might make the virus more infectious, or better able to avoid the immune system that is trying to counter them, either driven by natural infection or stimulated by a vaccine.

SARS-CoV-2, the virus that causes COVID-19, is no different. Each time it divides, it rolls the dice, which could give rise to a more malign virus. This can happen anywhere, anytime. So it’s important to track variants and to see if they are spreading more easily from person to person, causing more mild or more severe disease, might avoid detection with current tests, or might respond less well to current treatments. Perhaps the biggest concern is breakthrough infections, where a fully vaccinated person still gets COVID.

Once a variant is spotted, it is classified as being either a variant of interest, a variant of concern or a variant of high consequence. Mercifully, we have yet to see a variant of high consequence, which are variants against which current medical measures are failing. But we have at least four variants of concern.

That designation means there is evidence of increased transmissibility, more severe disease, a significant reduction in antibody neutralisation or reduced effectiveness of vaccines or treatments. These are B117 (first identified in the UK), B1351 (first identified in South Africa), P1 (first identified in Brazil) and B16172 (first identified in India).

There is evidence that all of these have increased transmissibility and there is a good molecular understanding of why that is.

Increased transmissibility can be observed epidemiologically (in the population), but it’s also important to confirm in a lab why that particular variant of concern can transmit more readily. The spike protein, which is the part of the virus that latches onto a receptor on human cells called ACE2, has changed in each of these variants of concern, and the change has been shown in some of them to increase the virus’s ability to bind to ACE2.

Some lab studies have shown that antibodies made to target the original spike protein are less able to neutralise the spike protein in the variants of concern. But, more important, so-called real-world data (which, in this case, means assessing a situation where a vaccine against the older SARS-CoV-2 has been used, but a variant of concern is the main virus in circulation) has indicated that this doesn’t have a big effect on vaccine effectiveness against some of the variants.

A very hopeful study from Qatar showed that the Pfizer/BioNTech vaccine was 90% effective against B117 and 75% effective against B1351. The AstraZeneca vaccine showed 75% effectiveness against B117.

Vaccines highly effective against B16172

Public Health England has reported that both the Pfizer/BioNTech and AstraZeneca vaccines are highly effective against B16172. Pfizer/BioNTech reached 88% effectiveness, while AstraZeneca achieved a level of 60%. This lower effectiveness for AstraZeneca might be because the rollout of the second shot of AstraZeneca was later than Pfizer/BioNTech. This study is important because it looks as though the B16172 variant may well become the dominant variant globally, replacing B117.

These analyses are all concerned with the risk of infection. The most important question, however, when it comes to the possibility of variants breaking through a vaccine is not whether someone gets infected, but whether that infection progresses to severe disease or death.

A vaccine’s job is to stop severe disease – and so far it is a reasonable prospect that the main vaccines in use should be able to do that against the variants of concern. This is probably partly due to the strong antibody response elicited by each vaccine. Even though the quality of the antibodies might be less, antibodies can make up for that with quantity. Think of antibodies as Blu-Tack. They can stick to the spike protein, and although they can get less sticky, the more there is, the more will stick.

And even if the power of antibodies were to be diminished, the immune system has another trick up its sleeve: T cells. T cells will recognise many parts of the virus (these are called epitopes). One recent analysis has concluded there are around 1,400 of these targets on SARS-CoV-2. On recognising a part of the virus, T cells can do two things: they can help the B cells to make lots of antibodies, or they can kill the infected cell. The killer T cell response might well kick in after the infection has started. The chances of T cells failing against variants is low. All of this should give us confidence.

Scientists are also trying to predict how much of an antibody response is needed to ensure protection against variants, to get a good idea of the risk of vaccine failure. Perhaps most importantly of all, it will be possible to vaccinate with booster shots with spike protein or mRNA from variants of concern, and there are even moves afoot to come up with a vaccine to protect against all coronaviruses. The pharmaceuticals company Novavax is even testing a combined flu/COVID vaccine.

There is always the chance of other variants of concern emerging. More malign ones may crop up, although that is difficult to predict, so it’s critical that we get vaccines to the countries that need them most, to forestall the possibility of more dangerous variants cropping up. What we’re also learning is it’s important to have the second shot of the vaccines that require them. The one-shot Johnson and Johnson vaccine might well need a booster, too. A third booster shot for the other vaccines might work too, as that will bring out a huge antibody and T cell response.

It’s clear what needs to be done when it comes to these variants: keep hunting for them, ensure universal vaccination and get ready for booster shots.

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