This paper analyses the antibody responses to vaccination and to natural Covid-19 infection illness followed by vaccination.

It is a relatively small study (45 participants); but as detailed observations were available for all the participants, it is nevertheless very useful. It used laboratory techniques to measure the level of antibody response and the extent to which antibodies neutralised antigens, including spike protein from other variants.

To be clear, the study:

• Only looks at antibodies.
• Only looks at beta (B.1.351, S Africa) and gamma (P1, Brazil) variants.
• Does not look at cellular immunity.
• Does not use clinical outcomes, just lab measurements. It can be used to predict what clinical outcomes you might expect; but it did not measure these directly (and to do so would require a much larger study).

When you give a booster jab, you expect two things (among others) usually to happen to antibodies: to boost the quantity of antibodies in the bloodstream, thereby enhancing protection and, as antibody levels generally decline slowly and predictably with zero-order (straight line) decay, increasing the duration of protection; and you expect the range of antigens (or, strictly, of epitopes – the parts of the antigen(s) the antibodies bind to) to increase. (You also expect to see improvements to the cellular immune response.)

But these do not always occur, so this study helps to confirm that they do usually occur for SARS-CoV-2 viruses.

Natural infection has a very similar effect to vaccination. For some reasons, natural infection does not always induce as strong an immune response as vaccines do; but it will nearly always induce a broader immune response, as the immune system is exposed to all of (in this case) the virus’ antigens, not just the ones chosen for the vaccine. This may be an advantage when variants arise, as the immune system may recognise and attack parts of the virus which are not included in the vaccine.

The study confirmed, as you might expect, that the immune response to natural infection followed by a dose of vaccine is at least as good as the response to two doses of vaccine; and also that the breadth of immunity increases with additional doses of vaccine, even if the vaccine does not contain the antigens in variants of the virus, thereby increasing antibodies’ ability to recognises and neutralise viral variants.

Note that the delta variant was not included in this study – presumably the bulk of the work was done before this variant became prevalent. Nevertheless, the message – that repeat vaccination increases the immune system’s ability to recognise and respond to other variants – is likely to apply, at least to some extent, to other variants.

The context is that the UK currently plans (if JCVI recommends it) to provide an additional booster dose to people in the UK who have already received two doses of vaccine. This paper did not, as far as I can see, investigate using a third (additional booster) dose of vaccine (although, reading the press release, you might think it did); but the finding that additional doses tend to broaden the immune response is encouraging, and might add to the reasons for giving this extra dose.

Note, however, that while this study adds to the rationale for considering giving and additional dose, it does not add anything to the question of whether such a dose is needed – or needed yet. We have seen that two doses of vaccine (with or without prior natural infection) are already very effective at preventing severe illness (hospitalisation, critical care admission and death). The priority must still be to give first doses to as many people in the world as possible, then to give second doses, and only then to consider booster doses. UNLESS there is vaccine to spare, in which case the additional dose might provide marginally better protection against infection with viral variants, and possibly enhance secondary protection by increasing the effectiveness of the vaccine at preventing people from being infected at all, and from infecting others.

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This study shows that the concentration and breadth (in terms of recognising different virus variants) of the neutralising antibody response to SARS-CoV-2 increases with increasing numbers of exposures to the virus, be that by vaccination alone or by a combination of natural infection and vaccination. This suggests that boosters are potentially beneficial and are unlikely to do any harm.

However, the study doesn’t tell us how big the benefit of an additional booster will be in people who have already had two doses of vaccine. In other words, will it make a material difference to the likelihood of becoming infected or passing the virus to others, or of becoming seriously ill or dying? This is actually what we need to know in order to decide on the most effective vaccination strategy over the next few months.

These data will emerge over the next weeks and months as we continue to monitor infection rates in the community and admissions to hospital.

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