Slight waning of immunity from vaccine could help to explain rise in 'double vaccinated' measles cases
The MMR vaccine remains the best protection against measles, according to a modelling study in England which suggests the level of protection decreases slightly over time.
MMR remains highly protective against measles for life, protecting over 95% of vaccinated individuals from measles.
However, a rise in measles infections among people who have had two doses of MMR is in line with the effectiveness of the vaccine decreasing by 0.04% each year after vaccination, the study suggests.
According to UKHSA data the proportion of measles cases in adults who had previously received two doses of the MMR vaccine ('double vaccinated') in England tripled from 1.9% (20/1064) to 7.2% (57/790) between 2011 and 2019. The reasons behind this rise were unclear.
Researchers at the London School of Hygiene & Tropical Medicine (LSHTM) used mathematical modelling to examine whether the rise could be explained by the small proportion of people who do not gain protection from MMR after two doses, or whether waning protection from the vaccine might also be a factor.
The team's findings, published in The Lancet Public Health, show that while the vaccine remains highly protective, a mathematical model with very gradual waning in protection from MMR could best reproduce the real number and age distribution of recent cases of measles in double-vaccinated people in England.
Lead author Dr Alexis Robert, Research Fellow in Infectious Disease Modelling at LSHTM, said: "Although our results suggest that a slight waning of immunity from the MMR vaccine over time explains why we are seeing an increase in the proportion of measles cases in double-vaccinated people in England, it's important to note that the biggest risk factor for measles outbreaks by far is low vaccination rates.
"The MMR vaccine remains highly effective and receiving two doses will protect you and those around you against measles infection.
"Even if you are one of the small number of people who get an infection after two doses of MMR vaccine, previous studies suggest measles symptoms in people who have been vaccinated are milder than in people who have not had a vaccine.
"This 0.04% waning each year is relatively slow, but because measles is so infectious, over time, this would add up to a 'gap' in a population's defences the virus can exploit, which may increase the duration and size of outbreaks."
More than 95% of individuals gain immunity after a single dose of MMR vaccine. This means that after two doses, only a small proportion of vaccinated people may be infected because of a lack of immune response. Due to this, it is expected to see a small proportion of measles cases in vaccinated people during outbreaks.
To assess the reasons behind the recent increase in proportion of measles cases in double-vaccinated people in England, the authors modelled three possible scenarios:
1. No vaccine waning immunity.
2. Waning of immunity (i.e. loss of protection) increases each year from the age of five (as almost all vaccinated individuals have received their second dose by then).
3. Individuals vaccinated before 2000 have full protection until 2000 (when measles was considered no longer endemic in England) but waning of immunity increases each year from the age of five after 2000. In this scenario, immunity in younger groups generally comes only from vaccination, rather than from vaccination and exposure to the virus.
The researchers then compared each scenario with the real confirmed measles cases in England between 2010 and 2019 to see which scenario best fitted the reality. No modelling was done to forecast future outbreaks.
Out of the three modelled scenarios, the two scenarios containing waning of immunity from the MMR vaccine best matched the real distribution of cases of measles in double-vaccinated people by age group and over time. In these two scenarios, vaccine effectiveness remained high after several decades but there was an estimated very slow decrease in effectiveness over time. In the third scenario, where waning immunity starts when measles is no longer endemic, vaccine effectiveness reduced by approximately 0.04% per year.
For someone born in 1995 who received two doses of the MMR vaccine before age five and gained full protection from the vaccine, a waning of about 0.04% each year would mean vaccine effectiveness remains on average:
• 99.6% at age 15
• 99.2% at age 25
• 98.8% at age 35
• 98.4% at age 45
In all scenarios, the authors included a risk of infection in the very small proportion of individuals who did not gain immunity upon vaccination. The results show that this was not sufficient to explain the increase in double-vaccinated cases observed in England, and adding a slow decrease in vaccine effectiveness helped capture measles transmission.
The findings could be partially explained by better access to testing and improved reporting among highly vaccinated groups which would increase the number of reported measles cases among highly vaccinated groups. However, as the increase was consistent through time, observed through multiple outbreaks and age groups and not restricted to a single group, the data suggest a biological explanation such as waning of immunity is involved.
Although finding only a small decrease in vaccine effectiveness over age, the model suggests this waning of immunity is enough to have an impact on the proportion of vaccinated measles cases among people infected with measles. The impact of waning is due both to the risk of a vaccinated person becoming infected, and the risk of transmission from vaccinated cases since individuals infected by vaccinated cases may not have been infected without waning. The model found that the risk of onwards transmission from double-vaccinated people was 83% of the risk of onward transmission in unvaccinated people, so that vaccinated cases are only slightly less likely to transmit than unvaccinated cases.
The researchers stress that everyone getting two doses of MMR vaccine is the best way to protect children and adults against measles outbreaks. As measles is so infectious the researchers say the slow waning of immunity is enough to open a 'gap' in our defences contributing to measles outbreaks. Maintaining high levels of vaccine coverage would be essential to mitigate the risk of transmission brought by a slow waning of immunity.
The latest UKHSA figures show only 85% of under-5s in England have received two doses of MMR, when the WHO target is 95%.
Co-author Dr Anne Suffel, from LSHTM, said: "Our study looks at one small part of the picture of measles cases in England. By far the larger issue in terms of measles spread is that uptake of the MMR vaccine has been decreasing in England since 2015.
"Understanding the impact of vaccine immunity waning will help anticipate the potential impact of measles in countries where incidence has been low for decades, but vaccine uptake is reducing. The best way to limit the impact of measles and protect everyone from what can be a horrible disease, is to keep vaccine uptake as high as possible."
Dr Adam Kucharski, Professor of Infectious Disease Epidemiology, co-author from LSHTM, said: "Our findings show that the measles dynamics observed in England are consistent with a slow waning of immunity in double-vaccinated individuals.
"Other factors may partly explain the increase in the proportion of vaccinated cases, such as changes in testing patterns over time. However, the consistency and age distribution of the increase in England - combined with reports of cases in vaccinated individuals in other countries and previous laboratory studies showing a decline in measles antibodies - suggests a biological explanation is involved."
Dr Robert said: "It's important to emphasise that the patterns we see in the data are only there because outbreaks have occurred as a result of declines in vaccine coverage. If there were no outbreaks, this small amount of waning would not show up in any data. The key issue here is coverage, not the effectiveness of the vaccine."
The authors acknowledge some limitations of the study, including that the scenarios represent a simplified version of reality so cannot factor in everything which may impact the spread of a disease, and that the accuracy of the model depends on the quality of the vaccination data it is based on. Additionally, measles outbreaks in countries close to elimination status are triggered by cases of disease in areas or communities where vaccine coverage is low, the model is unable to identify these pockets of susceptibility and therefore it would be inappropriate to use it to estimate the future risk of outbreaks. Finally, the authors recognise that testing patterns may have changed between 2011 and 2019, leading to improved identification of vaccinated individuals when they are infected, which could increase the proportion of double-vaccinated cases. Without access to testing data the authors could not test this assumption.
The research was an independent academic study supported by the National Institute for Health and Care Research and Wellcome.
Publication:
Alexis Robert et al, Long-term waning of vaccine-induced immunity to measles in England: a mathematical modelling study. The Lancet Public Health. DOI: 10.1016/S2468-2667(24)00181-6
