Study: MMR vaccine remains the most effective measure to prevent measles infection

The LancetSep 26 2024

Most measles cases in England are among unvaccinated individuals. But, between 2011 and 2019, the proportion of measles cases in adults who received two doses of the MMR vaccine in England increased from 1.9% (20/1064) to 7.2% (57/790), however the cause of this increase remains unclear. A new retrospective modeling study, published in The Lancet Public Health journal, suggests slow MMR vaccine waning may partially contribute to rising measles cases in double-vaccinated people when outbreaks occur. However, study authors emphasize that the MMR vaccine remains the most effective measure to prevent measles infection, and that community vaccination levels above 95% are essential to prevent outbreaks in the first place.

Measles is a highly contagious disease, spread by a virus which is easily transmitted when an infected person breathes, coughs or sneezes. Measles can infect anyone but is most common in children and can cause severe disease, complications, and even death. Having two doses of the MMR vaccine before the age of five is the best way to protect against measles over the lifetime. Unlike some other viruses, the measles virus does not mutate very much over time, and therefore effectiveness from childhood vaccination remains high throughout the lifecourse.

Following high uptake of measles vaccines, countries in Europe, the Americas and Asia observed a substantial reduction in the number of measles cases, with consecutive years without local measles transmission and only sporadic outbreaks. However, these countries reported a resurgence of measles cases between 2015 and 2020, with outbreaks increasingly affecting young adults in Europe. The majority of cases were in communities with low rates of vaccination, but the proportion of measles cases in double-vaccinated people has also increased.

In 2011 in England, 20 individuals who were double-vaccinated were infected with measles (1.9% of all cases) compared to 989 unvaccinated people (93% of all cases) whereas in 2019 in England, 57 individuals vaccinated twice had measles (7.2% of all cases) compared to 666 unvaccinated people (84% of all cases). 

More than 95% of individuals gain immunity after a single dose of MMR vaccine. This means that after two doses, a small proportion of vaccinated people (less than 1%) may be infected because of a lack of immune response. Due to this, it's expected to see a small proportion of measles cases in vaccinated people. 

However, it is unclear why there has been an increase in this proportion since 2010. There are thought to be two main possible explanations: 

• As the proportion of people who gained immunity from a vaccine rather than from a much riskier infection increases, the proportion of cases coming from rare events where both vaccine doses resulted in a lack of immune response is also expected to increase.
• Waning of vaccine-induced immunity. 

This study is the first to use mathematical modeling to suggest measles cases and spread in England are consistent with a small amount of waning of vaccine-induced immunity.

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." 

Dr. Alexis Robert, The London School of Hygiene & Tropical Medicine

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: 

• No vaccine waning immunity.
• Waning of immunity increases each year from the age of five (as most vaccinated individuals have received their second dose by then).
• 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. 

All scenarios included the risk of rare infections in double-vaccinated individuals who did not gain immunity when vaccinated. 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 modeling was done to forecast future outbreaks.

Out of the three modeled 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 is 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 

People who have been vaccinated remain highly protected from measles. In the rare cases of a vaccinated person becoming infected with measles, previous research suggests their symptoms would likely be milder than people who have not received a vaccine, but they could still transmit the virus - in this study, the risk of onwards transmission from rare cases of measles among vaccinated individuals was 83% that of unvaccinated individuals. 

"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," says Dr Anne Suffel, The London School of Hygiene & Tropical Medicine. 

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, as 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 recognize 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.

"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." says Dr Adam Kucharski, The London School of Hygiene & Tropical Medicine.