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expert reaction to modelling study looking at whether protection against measles from the MMR vaccine decreases over time

A modelling study published in the Lancet Public Health looks at long term MMR vaccine waning.

 

Prof Alex Richter, British Society for Immunology spokesperson and Director of the Clinical Immunology Service, University of Birmingham:

“The paper by Robert et al. provides further insights into the increasing cases of measles seen in the UK and globally.  Mathematical models of epidemiological data suggested that at least some of the increase in measles could be explained by waning of immunity following vaccination.  Our national vaccination programme assumes that two doses of MMR vaccination does provide life long immunity and this paper challenges that assumption.  However, most measles cases are in the unvaccinated and in children under the age of 15.  When looking at the UKHSA measles dashboard, there is no trend of increasing cases the further someone is in time from vaccination which goes against the waning of immunity as being a main driver for increasing measles cases.  Also, the model assumes that everyone responds equally to the vaccine and we know for example that many immunosuppressed patients may not respond optimally.

“Low vaccine uptake likely has a more significant role in increased measles cases, with uptake rates below 90% particularly in younger age groups (Ho et al. Lancet).  However, to determine the true role of waning, immunogenicity studies will be required to assess the short and long term immune response following vaccination.

“It’s still important to remember that measles is a nasty infection that can make you very ill.  In the current UK outbreak, one in five children who contract measles are hospitalised.  Making sure you and your children are fully up to date with both doses of the MMR vaccine is still the safest and most effective way to protect you and your family from catching measles.  If someone is uncertain whether they have been vaccinated, they can check with their GP and request a catch up vaccine if necessary.”

 

Dr Louise Dyson, Associate Professor (Reader) in Epidemiology, University of Warwick, said:

“The MMR vaccine is highly effective at preventing measles cases, but because measles is very infectious, high levels of vaccination are required to prevent major outbreaks.  This research implies that the initial high protection afforded to double-vaccinated individuals wanes slowly over time, with efficacy decreasing by 0.04 percentage points per year.  This means that an initial 98% efficacy may wane to 96.8% efficacy 30 years later.  These estimates are made by fitting a mathematical model of infection, with and without immune waning, and observing that the model with waning is more consistent with the data.  It is always difficult to ensure all the relevant mechanisms are captured well enough to make reliable estimates, but in my opinion the modelling in this paper is good quality.

“Note that the press release which claims “vaccine effectiveness remains on average 99.6% at age 15” etc. is a bit confusing, as it assumes 100% effectiveness at the time of vaccination, whereas the study finds 98% efficacy at primary vaccination.  We can compare this to a 2020 Cochrane review, which found two doses of MMR vaccine to have effectiveness of around 96% in preventing measles.”

 

Prof Sir Roy Anderson FRS FMedSci, Professor of Infectious Disease Epidemiology, Imperial College London, said:

“At present the key issue is vaccine uptake in the UK (and indeed in many other countries), which is at far too low a level.  The second important issue is the age at which children are vaccinated.  This need to be as close to 2 years of age as possible.

“Loss of vaccine induced immunity over time is very low in the estimates presented in this paper, which employs models that are relatively simple.

“Both points are made by the authors – but the greatest emphasis in the paper is placed on loss of vaccine induced immunity – not the more important issues of vaccination coverage and age at vaccination.”

 

Prof Thomas House, Professor of Mathematical Statistics, University of Manchester, said:

“This study considers the possible impact of waning of vaccine immunity to measles in explaining the observation that an increasing proportion of measles cases are vaccinated, although this is still a small minority of cases, and we have to keep in mind that the overwhelming majority of people are vaccinated.  As the study press release says, the MMR vaccine remains highly protective against measles for life.  As with all studies based on observational data, there is the possibility of confounding, however when a mathematical model is used that accurately captures basic scientific knowledge of the disease system – as has been done here – then that becomes less likely.  It has been known for some time that for a disease as infectious as measles, that the period of extremely low infection rates seen after the rollout of MMR – sometimes called the ‘honeymoon period’ – would eventually end due to accumulation of a large enough susceptible population, and indeed we have seen measles re-emerge in the UK although at nothing like its pre-vaccination intensity.  This was initially hypothesised as being due to lack of natural immunity with the disease not circulating, but the current study shows that waning vaccine immunity is also likely to play a role, although this study suggests any waning is slow and slight.  As always with measles, the higher vaccine uptake is, the better, and it is increasing MMR coverage that is generally believed to be the main intervention that we should consider in response to measles as a health threat.”

 

Prof Sir Andrew Pollard FMedSci, Ashall Professor of Paediatric Infection and Immunity and Director of the Oxford Vaccine Group, University of Oxford, said:

“This new publication provides an interesting framework to think about measles transmission dynamics which may be useful for academic discourse.  It is a modelling study which by definition uses assumptions which may or may not be correct and cannot capture the complexity of the real world.  But in the real world measles cases are on the rise across the globe because children are just not getting jabbed.  Most of the problem is the simple inadequacy of health systems, including the NHS, to connect with families, provide knowledgeable advice and ensure easy access to measles and other life-saving vaccines.  It is a fact that measles goes away when at least 95% of children are consistently vaccinated in a population and achieving this will stop the ongoing and future outbreaks here in our communities – we must fix this for our children.”

 

Dr David Elliman, Community Paediatrician and Consultant, Great Ormond Street Hospital; and Clinical Advisor to UK National Screening Committee & NBS Screening Programme, said:

“This is a complex modelling study looking at whether the protective effect of MMR vaccination against measles wears off over time.  Infectious disease modelling is a complex process and for most of us, it would be difficult to comment on exactly how well the modellers have addressed this issue.  The London School of Hygiene and Tropical Medicine is well known for its modelling of infectious diseases, so there is no reason to believe the modelling is not accurate, though it is based on a number of assumptions, which, for all I know, may be absolutely correct.

“However, it is worth looking at their conclusions and the implications.  They suggest that the protection from measles provided by the MMR vaccine does indeed decline with time, but by a very small amount – 0.039% per year.  Two doses of MMR usually lead to well nigh 100% protection.  Using the authors estimates, this means that at age 45 years, someone who had had 2 doses of MMR in early childhood would have approximately 98.4% protection at 45 years old.  That sounds very good to me and obviously an enormous amount better than no vaccine.

“The trouble with measles is that it is very infectious and the uptake of MMR is steadily falling.  This means that the number of cases of measles has gone up considerably and sadly we have already seen a death due to this – an adult visiting from Ireland who caught measles while here and died back home.

“It is vital that we reverse the downward trend in uptake by reassuring parents that the scientific evidence consistently shows that the vaccine is very effective (as shown by this research) and has a good safety record.  It would be a tragedy if we see more deaths from this eminently preventable disease.”

 

Prof Adam Finn, Professor of Paediatrics, University of Bristol, said:

“This is an interesting and good quality modelling paper, which explores different theories about ways in which population immunity to measles may be changing over time as the proportion of people immune due to vaccination rises compared to the proportion immune by having had measles, which was much more common in times gone by.  Although it’s clear that two doses of measles vaccine are highly effective at protecting against measles, the modelling suggests that this protection may reduce very slowly as time passes at least in some people, meaning that they may get measles and pass it on to others if exposed.  The implication of this modelling is that it is even more important to achieve and maintain high two dose coverage with MMR in all areas of the country if we are to stop measles outbreaks from occurring and protect ourselves from the dire consequences of this dangerous but entirely preventable disease.”

 

 

‘Long-term waning of vaccine-induced immunity to measles in England: a mathematical modelling study’ by Alexis Robert et al. was published in the Lancet Public Health at 23:30 UK time on Thursday 26 September 2024.

DOI: 10.1016/S2468-2667(24)00181-6

 

 

Declared interests

Dr Louise Dyson: “I have no conflicts of interest to declare.”

Prof Alex Richter: “No interests to declare.”

Prof Thomas House: “I don’t think I have any relevant conflicts of interest here.”

Prof Sir Andrew Pollard: “AJP is chair of the Joint Committee on Vaccination and Immunization (JCVI).  AJP was a contributor to the development of the Oxford-AZ vaccine.”

Dr David Elliman: “I have no conflicts of interest.”

Prof Adam Finn: “Adam Finn is an unpaid adviser to the UK government and was formerly to the WHO concerning vaccine policy; leads research related to vaccines for the University of Bristol which is funded by vaccine manufacturers; and does paid consultancy for companies which develop and manufacture vaccines, including some which market measles-containing vaccines.”

For all other experts, no reply to our request for DOIs was received.

 

This Roundup was accompanied by an SMC Briefing.

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