Q&A on What is Happening to COVID-19 Immunity

Please note that these answers are accurate at the time of writing, but this is a rapidly advancing area of study.

What has been the effect of COVID-19 vaccines on transmission and infections, hospitalisations, and deaths?

Transmissions: If you have been fully vaccinated your chance of being infected with COVID-19 infection is approximately halved. Further to this, if you do get infected, you are also half as likely to pass it on. Therefore, vaccination reduces viral transmission overall by 75%

Hospitalisations: Two doses of the Pfizer/BioNTech or Oxford/AstraZeneca vaccine were estimated to be 96% and 92% effective against hospitalisation with the Delta variant, respectively. The effectiveness varies with age (see below)

Deaths: ONS data shows that between 2 January and 24 September 2021, the age-adjusted risk of deaths involving COVID-19 was 32 times greater in unvaccinated people than in fully vaccinated individuals.

What is the difference between immunity and vaccine effectiveness?

Immunity can be used in a variety of contexts. At an individual level it is the competence of your immune system to fight off a virus (or other pathogen) challenge after it has been educated by an initial challenge – either from the virus itself or from a part of the virus in the vaccine. We can have varying levels of immunity depending how effective our immune systems are. If the level is high enough and in the right place in the body, it will stop an infection completely. Even if it can’t completely stop an infection, it is very often high enough to stop severe disease. Immunity is also used as a broader term at a population level taking into account levels of individual immunity together with proportions of the population with individual immunity over an assumed protection level.

Vaccine effectiveness is a measure of how effective a vaccine is at preventing infection/symptoms/hospitalisations/deaths at a population level under real world conditions where behaviours and population heterogeneity are not controlled (as opposed to vaccine efficacy which is measured in clinical trials under more controlled conditions).

What are the factors affecting COVID vaccine effectiveness?

There are many different factors affecting the effectiveness of a vaccine: the type of vaccine used (e.g. AZ versus Pfizer), the interval between vaccine doses (e.g. 3 weeks versus 12 weeks), the time since the vaccine was administered (e.g. if there is any change in immunity over time), the age of the recipient (e.g. the rate of immune loss changes with age), the exposure to the virus (e.g. low doses from brief encounters in well ventilated environments with masked individuals versus higher doses from longer encounters of unmasked individuals indoors), the variant of SARS-CoV-2 in circulation (e.g. Alpha versus Delta). We are gradually finding out more about these factors, for example, in people who had a greater length of time between receiving their first and second vaccine doses, the peak level of antibodies was slightly higher compared with those who had a shorter gap between doses. Those aged over 70 years had a substantially quicker decline in antibody levels if they had received their second vaccination only three weeks after their first.

Is measuring vaccine effectiveness becoming more difficult?

Does immunity change over time?

Can a vaccine booster programme increase immunity?

Yes, it can. In Israel for example, rates of infection and severe illness were substantially reduced after a booster dose over a range of age groups. Early indications are that this will also be the case for the UK population.

Although the data can be confounded by the different times at which people of different ages were vaccinated, early indications are that immunity wanes faster in older people, men, those reporting white ethnicity and those with long term health conditions.

Is immunity being lost in the UK before other countries because our vaccine rollout began sooner?

We can’t say. Infection rates and death rates seem to be very different in different countries, although since the definitions of cases and deaths and the amount of asymptomatic testing going on vary so much in different countries, it is very difficult to compare. Also, different age groups in different countries are currently experiencing the highest infection rates and the timing of rollout of the vaccine to different age groups again varied from nation to nation. Given all this heterogeneity, it is almost impossible to compare, and we must be careful not to make assumptions based on inappropriate metrics.

Do you get better immunity after COVID vaccination or COVID infection?

It depends on how you define “better”. One problem is that immunity after infection is very variable whereas immunity after vaccination is more predictable. Nevertheless, infection does confer some immunity and data suggests that it is on par with the immunity conferred by vaccines when the Delta variant is the predominant strain, but not when the Alpha variant dominated. It is unclear however whether this is because of the different variant, waning immunity, or because many unvaccinated people are younger.

Immunity after infection may be more broadly based (targeting the whole virus not just the spike protein) and therefore may cope better with variants, but depending on the nature of your infection, it may be quite feeble and short lived. So, just because you have been infected you cannot simply assume that you are fully immunised.

Importantly, the evidence is that people who have been infected respond very well to the vaccine, and the vaccine is very safe in people who have previously been infected. So, whatever your prior experience with COVID-19, it is always worth getting vaccinated.

How effective are COVID-19 vaccines in people with weakened immune systems? Will the booster work in these people?

We know that some people with weakened immune responses make lower antibody responses after vaccination, but other people respond very well. Similarly, some immune compromised people make weaker T cell responses but others make very good T cell responses. It rather depends on what the underlying condition is, i.e. which bit of the immune system isn’t working as well as we would like,   or which drugs you are taking, i.e. which bit of the immune system is being suppressed.

It is likely that a third dose of vaccine will help the majority of these people, and trials are underway to look at this. For example, in kidney transplant and dialysis patients, who are known to have poor responses to initial mRNA vaccine, a booster mRNA vaccine increased the proportions of patients with protective levels of antibody from 34% to 93% (dialysis) and from 11% to 58% (transplant).

The numbers of COVID-19 infections and deaths in any particular clinical group, where they may still be shielding, may be too small to be certain whether they are less protected than healthy people. This means that any estimates we make have a high degree of uncertainty.


What are the benefits of vaccinating children – why is this important?

A very recent clinical trial with the Pfizer/BioNTech vaccine in 5-11 year old children reported that the vaccine was safe, induced good antibody responses and demonstrated a vaccine efficacy of ~90% in preventing infection. This suggests that vaccinating children will have substantial benefits in preventing cases, concomitant long COVID, and disruption to their education and recreational activities. Massively reduced infections will also have a major impact on the spread of the virus throughout the community. The vaccines don’t completely block transmission, but they do reduce it – so vaccinating a large percentage of children should help to reduce the case rates in their parents’ and grandparents’ age groups.

If we haven’t had a major variant of concern (VOC) appear since Delta last April, does that mean there’ll be no more variants?

It is very reassuring that no variant more infectious than Delta has spread yet, but we shouldn’t assume that there won’t be another more infectious variant. Consequently, we need to maintain genomic surveillance and quickly investigate any localised spikes in transmission in order to provide an early warning.

We’re being boosted with 1st generation spike vaccines, but what about vaccines expressing VOC sequences?

If the Delta variant really is as bad as it gets, then a next generation COVID-19 vaccine specifically targeting the spike protein of Delta may help to reduce the prevalence of cases. Unless, however, it blocks transmission very effectively, it may not have much impact on the number of cases beyond what we can achieve presently with the 1st generation vaccines.