January 21, 2021

expert reaction to a preprint on vaccines and herd immunity

A preprint, an unpublished non-peer reviewed study, looks at immunisation, asymptomatic infection, herd immunity and the new variants of COVID-19.

Prof Mark Woolhouse, Professor of Infectious Disease Epidemiology, University of Edinburgh, said:

“The UEA preprint rightly raises the possibility that it will not be possible to reach the herd immunity threshold for novel coronavirus through vaccination alone.  This has been recognised by epidemiologists for some time.

“Whether the threshold is reached on not depends on several factors.  First, how well the vaccines prevent infection or how much they reduce infectiousness (among those who get infected despite being vaccinated).  Second, it depends on coverage – the proportion of the population who are offered the vaccine and take it.

“Even if it is not possible to reach the herd immunity threshold, the more we can reduce transmission rates the better – this will make the virus easier to control by other means.

“The best vaccination programmes typically achieve coverage of 90-95%. Many of those who – for whatever reason – do not get vaccinated tend to be minorities and the disadvantaged.

“It is vital – for their sakes and everyone else’s – that these groups are not left behind as vaccination is rolled out.”

Dr Peter English, Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice Magazine, Immediate past Chair of the BMA Public Health Medicine Committee, said:

“The proportion of the population that has to be vaccinated depends (among other factors) on how infectious a disease is. For measles, for example, R0 is approximately 18. This means that, on average, if nobody in the population is immune, and no other measures are in place to reduce transmission, each person with measles will infect 18 other people. If it’s 10 days from one person in a chain of infection to the next one being infected, then every 10 days the number of people with measles will multiply by 18. But if some of the 18 people that a particular case would have infected were already immune, they will infect fewer than 18 people – the others being protected.

“As soon as more than 17 out of every 18 people (on average) are immune, each person with measles will infect fewer than one other person, and any outbreaks will quickly fizzle out.

“So, for measles, we need to ensure that >17/18 of the population is immune. After two doses of vaccine 99% of the people vaccinated will be immune – unable to be infected, and to pass the infection on to others.

“With Covid-19, the same principles apply. Even with the new, more infectious variants, Covid-19 is much less infectious than measles – R0 is probably of the order of 5. In order to achieve herd immunity, we would want >4/5 of the population to be immune and not susceptible to becoming infected.

“But with Covid-19, we don’t know how effective the vaccine is. Vaccines may be able to:

1. Prevent severe disease;

2. Prevent less serious symptomatic disease;

3. Prevent infection (and thus stop people from carrying the pathogen and passing it on to others). 

“Most vaccines are decreasingly effective as you work down this list. We see this from the preliminary data on Covid-19 vaccines: they are more effective at preventing serious infection requiring hospital admission than they are at preventing less severe infections. This is the case for influenza vaccine, by the way. ‘Flu vaccine efficacy varies according to how good a match there is between the vaccine and circulating strains (and a whole load of other factors); but while its headline efficacy may be, say, 50%, its efficacy in preventing hospital admission or death is usually much higher.

“In order to get the herd immunity (sometimes referred to as population immunity or indirect protection) benefits of vaccination, a vaccine needs to prevent infection and transmission.  For the Covid-19 vaccines, we don’t yet have good quality data on their efficacy in preventing infection and transmission to be able to draw firm conclusions on this. We expect to get more detail on this from the post-implementation (aka post-marketing) surveillance undertaken by PHE and others.

“This new study uses very preliminary data, and attempts to compare vaccines which have not been properly compared ‘head to head’. While it raises important issues – many of the predictions about ‘going back to normal’ seem to presuppose that the vaccines will prevent infection and transmission, not just disease – I would be disinclined to be put to much credence in the specific conclusions. We simply do not know enough about vaccine efficacy in terms of preventing infection and transmission.”

Dr Stephen Burgess, Programme Leader at the MRC Biostatistics Unit, University of Cambridge, said:

“In the preprint “Immunisation, asymptomatic infection, herd immunity and the new variants of COVID 19”, Grant and Hunter ask the question whether herd immunity is achievable by immunization alone assuming pre-pandemic behaviour. They use a combination of estimates and extrapolations to conclude that it is not possible to achieve herd immunity by immunization alone. While the authors make several extrapolations and assumptions, this answer is perhaps reasonable. However, it is not the answer to a meaningful question.

1. It is unlikely that we will return to pre-pandemic behaviour any time in the near future. Even when social restrictions are relaxed, this will happen gradually and cautiously. 

2. Herd immunity will not be achieved by immunization alone, but by a combination of immunization and immunity from prior infection.

3. Even if herd immunity cannot be reached, this does not change the fundamental dynamics of the response to the current stage of the epidemic in the UK or in any other country. The aim is to vaccinate as many people as possible so that as many people as possible achieve immunity via vaccination rather than via exposure to the virus. Given current availability of stocks, this is best achieved by using all available doses of all available vaccines.

“In short, this paper represents the right answer to a question that is at best irrelevant. Rapid vaccination remains the key to curbing the negative impact of the pandemic.”

Prof Azra Ghani, Chair in Infectious Disease Epidemiology, Imperial College London, said:

“The primary aim of the COVID-19 vaccines is to save lives. This will occur through the direct protection of those that are vaccinated – with both the Pfizer/BioNTech and Oxford/AstraZeneca vaccines currently being offered in the UK demonstrating high effectiveness, particularly against severe disease that could result in hospitalisation. Vaccines more generally can also save additional lives through indirect protection – reducing onward transmission in the community and therefore reducing the risk of exposure in both vaccinated and unvaccinated individuals.

“The herd immunity threshold is the level of the population that needs to be immune to reduce R below 1 and therefore eliminate circulating the virus. When the basic reproductive number (R0) is high, we need both high efficacy vaccines and a high uptake of vaccination across the population to achieve this threshold. As this preprint points out, with the more transmissible new variant, this is going to be challenging to achieve. However, it is important to note that this does not mean that we will be living with the current level of restrictions indefinitely. If a high proportion of those that are at risk of severe complications from the disease are vaccinated, then the number of hospitalisations and deaths will be dramatically reduced and the way we react to the circulating virus should become similar to the way that we react to other circulating viruses such as influenza. Furthermore, although the vaccines are not yet recommended for children, studies are underway and therefore it is likely that children could be vaccinated if that is considered necessary.  

“Given that it is only just over a year since the virus was identified, the progress that has been made in the development and roll-out of vaccines is unprecedented. The science of this new virus is still evolving and a large number of teams of scientists across the world are actively engaged in testing and improving vaccine candidates. I believe we can therefore be optimistic that with these efforts it will be possible to achieve high levels of both direct and indirect protection that, whilst not eliminating the virus, will allow life to return to normal.”

Dr Jonathan Stoye, Group Leader, Retrovirus-Host Interactions Laboratory, The Francis Crick Institute, said:

“This preprint, so far unreviewed, reports a modelling study examining the question of whether vaccine administration by itself will be sufficient to protect the whole population from SARS-CoV-2 infection.  Using current estimates of vaccine efficacy, the frequency of asymptomatic infections and taking to account recent increases in virus transmissibility, it compares the impact of the Oxford/AstraZeneca and BioNTech/Pfizer vaccines on virus spread.  It reaches the provocative conclusion that administration of the Adenovirus based vaccine from Oxford/AZ alone, despite a major reduction in the seriousness of COVID-19 disease, is unlikely to generate the herd immunity needed for complete control of virus spread.  Based on the data currently available, this study appears strong and the conclusion unarguable. It points to a continuing role for non-pharmaceutical interventions such as the wearing of face masks and hand washing as well as suggesting a possible utility for booster vaccinations with RNA based delivery systems.”

Prof Rowland Kao, Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, said:

“This analysis looks at the impact of the new variant on the likelihood of herd immunity and shows that the higher transmission rate means that even the very high efficacy vaccines means herd immunity would not be achievable.

“While this is useful to know, even in the absence of a more highly transmissible new variant of COVID-19, achieving herd immunity was likely going to be difficult. There are uncertainties regarding the duration of immunity and whether or not vaccinated individuals are able to transmit the virus. Further issues arise in that, like seasonal influenza, COVID-19 may evolve to vaccine-evading strains (something it may have already partially done, but becomes more likely as we vaccinate more individuals).

“On the other hand, herd immunity is not impossible, as it does not only rely only on vaccination, but also on naturally-acquired immunity which may have a greater protective effect; and the levels of natural immunity are not considered in this study.

“A further consideration not considered in this paper is that, post-pandemic, greater awareness of physical distancing and continued voluntary and ‘lighter touch’ measures may mean that the requirements for herd immunity may be lower. Thus it is likely that herd immunity is more difficult, even before the new variant, we were not in the position where planning for herd immunity has been wise. In particular, in order to get the number of cases down, the uncertainties we have mean that ongoing restrictions may continue even long after a large proportion of the population is vaccinated.”

https://www.medrxiv.org/content/10.1101/2021.01.16.21249946v1

Declared interests

Dr Burgess: “I have no relevant conflict of interest to declare.”

None others received.