A study in The Lancet Public Health in September 2024 evaluates the measles dynamics in England between 2010 and 2019 to understand the effects of waning of vaccine-induced immunity. The researchers find that, although the MMR vaccine remains “highly protective” against measles infections for decades, and most transmission is “connected to people who are unvaccinated”, breakthrough infections in vaccinated individuals aged 15 years or older are “increasingly frequent”. However, they emphasise the importance of adequate coverage alongside vaccine effectiveness.
In England, measles “follows typical near-elimination transmission dynamics”, with “sporadic localised outbreaks and high national vaccine coverage”. England reached measles elimination status after “large outbreaks” between 2011 and 2013. From 2017 onwards a resurgence has been observed.
Highly protective vaccines
The authors describe measles vaccines as “highly protective against infection” recognising that they enabled a “great decrease in the global burden of measles” after immunisation programmes began in the 1970s and 1980s. Indeed, some countries became eligible for an elimination status since 2000 after the successful implementation of routine immunisation programmes. However, this is slipping out of reach for many countries in Europe and the Americas, which have reported a resurgence between 2015 and 2020.
“This resurgence was mostly reported in under-immunised communities and linked to past variations in vaccine coverage.”
Further outbreaks have been reported in “highly vaccinated” groups in Portugal and Japan, inviting questions about the waning of measles immunity in adults who had received two doses in childhood. Research suggests a waning of antibodies in young adults who had received two doses of vaccine “more than 20 years earlier”, in contrast to no decrease in previously infected individuals. Analysis of outbreak data suggest a “drop” in vaccine effectiveness in young adults who had received two doses of vaccine. However, effectiveness estimates appear to be “sensitive to assumptions on infection-induced immunity”.
The study
The study addressed the need to understand whether the measles case dynamics of settings with high vaccine coverage result from a waning of vaccine-induced immunity or if changes in the distribution of immunity in the population are driving the distribution of vaccine status among cases. A mathematical transmission model, stratified by age, region, and vaccine status was used to evaluate whether the measles dynamics in England from 2010 to 2019 were “in line with a waning of vaccine-induced immunity”. Three scenarios were modelled:
- Vaccinated individuals might only become infected because of primary vaccine failure
- Vaccinated individuals might become infected because of primary or secondary vaccine failure, with the risk of secondary vaccine failure depending on age
- Vaccinated individuals might become infected because of primary or secondary vaccine failure, with the risk of secondary vaccine failure depending on age and time since measles stopped being endemic
Each scenario was fitted to measles case data reported in England between 2010 and 2019, and the authors compared the resulting performance. Data were collected by UKHSA (formerly Public Health England), and included date of symptom onset, region of residence, age, and vaccine status. The final case dataset included 7,504 cases. The annual proportion of individuals who had been infected with measles and received two doses of the vaccine out of the overall number of individuals with measles was three times higher in 2019 than in 2011. The median age of individuals with measles was 12.5 years.
Results
Scenarios integrating waning of vaccine-induced immunity “better captured measles case dynamics” than the scenario without waning. In the scenario where waning started in 2000, the estimated waning rate was 0.039% per year.
“Although slow, waning was associated with an increased burden over time; setting the waning variable in this scenario to 0 led to a substantial decrease in cases.”
While overall vaccine effectiveness was estimated to stay high over the decades, the estimation suggested that the increasing number of breakthrough infections contributed to the measles burden in England. The additional burden brought by waning is “directly related to the risk of transmission from vaccinated cases”, as individuals infected by people who had been vaccinated would not have otherwise been infected.
“Our results suggest that the waning of vaccine-induced immunity likely explains the observed dynamics and age distribution of vaccinated measles cases in England between 2010 and 2019.”
Low vaccination rates a bigger factor
Dr Alexis Robert, Research Fellow in Infectious Disease Modelling at London School of Hygiene and Tropical Medicine (LSHTM) drew attention to the “biggest factor for measles outbreaks”: low vaccination rates. Dr Robert emphasised that the MMR vaccine is “highly effective” and two doses “will protect you and those around you”.
“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.”
The data patterns in the study emerge “because outbreaks have occurred as a result of declines in vaccine coverage”, said Dr Robert.
“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.”
Dr Anne Suffel, co-author from LSHTM, agreed that the study “looks at one small part of the picture” and recognised that the “larger issue” 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 and co-author from LSHTM, acknowledged the role of “other factors” 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.”
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