How many COVID antibodies are enough?

Recently, the Joint Committee on Vaccination and Immunisation - outlined plans for an autumn booster programme to "top up" the immunity of everyone over 50 against Covid-19. But one thing that hasn’t been clear so far is how much antibody do I need in order to be protected; and why are some people, despite vaccination, still able to catch coronavirus infection but not become unwell? Now we have a bit more clarity, because as Robert Seder explained to Chris Smith, he’s done some careful experiments on monkeys, which develop Covid-19 infections in a similar way to humans. This has revealed the level of antibody that’s needed to protect both against severe lung disease and also against just catching - and potentially passing on - the infection. The two turn out to be different, and this means we now have a benchmark to aim for, when/if embark on a programme of booster doses this autumn…

Robert - When you give the vaccine, we're trying to measure the type of immune response in the blood that would tell you that you would be protected in the lungs or in the nose. You want to protect people first in the lungs, so they don't get severe disease. And you'd like to protect people in the upper airway, so it might prevent them from getting symptoms of a cold, and then you would not be able to give it to somebody else.

Chris - Was this not known already, given that we have put billions of doses of vaccines into the world's population so far?

Robert - There had been a couple of studies that showed that the higher levels of antibodies you had in the blood, a measure of the immune response, the better off you were for protection. So our study in animals provided greater specificity to really define exactly what the level of antibody response in the blood was to mediate protection in either the lung or the nose.

Chris - So this is sort of a way of standardising. When we give someone a vaccine of some type in particular, what's the threshold level of antibody we probably need in the blood either to protect their lungs or to protect their upper airways and therefore protect them either from just getting COVID or from transmitting the infection?

Robert - That's exactly right. And the reason why, if you have a precise measurement, is it would allow you, if people had their blood measured and you were immunocompromised, or you were older or had a pre-existing illness, if your antibodies were below that level, it might indicate that you're at greater risk and it might indicate that you would need another shot of the vaccine to put you above that threshold. So it can be very helpful in guiding perhaps people at greater risk or over a long period of time, whether your immune response is waning and you need a boost. It also helps you with other vaccine approaches where if they haven't gone through the full process of a large, phase three study, but their vaccine shows very high levels of those immune responses, you might be able to use the metric data to suggest that that vaccine is very likely to work and possibly being able to facilitate approval of another type of vaccine based on achieving that certain metric.

Chris - Does it shed any light on something we're increasingly seeing perhaps in the light of having a very high fraction of the UK population now vaccinated is that we seem to be seeing lots more asymptomatic infections and people are a bit surprised because they think, well, I've been vaccinated. How am I catching this thing at all? Do your results give us some insights into how that's happening.

Robert - Yeah, so I think one of the key findings of the study was that we showed that less antibodies or less immune response is required to protect you from severe disease in the lower airway than what is required in the upper airway. And I think that explains why all of the vaccines are very good at preventing severe disease. But you're now starting to see a differentiation of vaccines for protection against mild infection or asymptomatic infection, in the upper airway. And I think it would just make sense that you just need more of an immune response in the upper airway to limit infections, especially with something like the Delta variant, where there's a lot more virus in the nose. And so the better vaccines that induce higher immune responses, that translates into having higher responses in the upper airway, and so that's why a vaccine could protect you from going to the hospital, but might not protect you from mild infection or transmitting it.

Chris - Is one interpretation of your findings then that actually, if we drove everyone's immune response as hard as possible, we could get everyone to a point where they'd have enough antibody where they just couldn't be infected, and at the moment, we're just not doing that enough?

Robert - That's a very good point. And that is potentially the rationale for giving people another vaccination or a boost, is if you could boost antibodies higher, it might sustain your continued very high level protection against severe disease. Remember all vaccines are basically 90 to 100% protective. And so if you boost, you sustain that, but if you had more antibodies perhaps in your upper airway, might that serve to limit transmission? And when you look at the Delta variant, which is existing at probably a hundred- to a thousand-fold more virus in the nose, might that be the only way that you can accomplish that is with another boost to get higher levels of antibodies? The alternative in the future might be for things like COVID and upper respiratory infections is to have vaccines that might be given to induce immune responses directly in your upper airways, and might that be better? And I think that that will be an interesting area of research going forward.