Long-term waning of vaccine-induced immunity to measles in England
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Background
The proportion of double vaccinated cases during measles outbreaks in England has increased since 2010, especially among teenagers and young adults. Possible explanations include: rare infections in vaccinated individuals who did not gain immunity upon vaccination, made more common as the proportion of the population born before vaccination decreases; or waning of vaccine-induced immunity, which would present new challenges for measles control in near elimination settings.
Methods
To assess explanations for observed dynamics, we used a mathematical model stratified by age group, region and vaccine status, fitted to case data reported in England from 2010 to 2019. We evaluated whether models with or without waning were best able to capture the temporal dynamics of vaccinated cases in England.
Findings
Only models with waning of vaccine-induced immunity captured the number and distribution by age and year of vaccinated cases. The model without waning generated more single-vaccinated cases, and fewer double-vaccinated cases above 15 years-old than observed in the data (median: 73 cases in simulations without waning, 202 in the data, 187 when waning was included). The estimated waning rate was slow (95% credible interval: 0.036% to 0.044% per year in the best fitting model), but sufficient to increase measles burden because vaccinated cases were almost as likely to cause onwards transmission as unvaccinated cases (95% credible interval for risk of onwards transmission from vaccinated cases was only 7% to 21% lower relative to unvaccinated cases).
Interpretation
Measles case dynamics in England is consistent with waning of vaccine-induced immunity. Since measles is highly infectious, a slow waning leads to a heightened burden, with an increase in the number of both vaccinated and unvaccinated cases. Our findings show that the vaccine remains protective against measles infections for decades, but breakthrough infections are increasingly likely for individuals aged 15 and older.
Funding
National Institute for Health Research; Wellcome Trust.
Research in context
Evidence before this study
We searched PubMed up to February 29, 2024, with no language restrictions using the following search terms: (measles) AND (“secondary vaccine failure” OR waning) AND (antibody OR “vaccine effectiveness”), and excluded studies that focused on waning of maternal antibodies in infants. We found evidence of waning of antibody concentration in young adults from laboratory data, but this may not translate into a loss of protection against infection. We also found estimates of vaccine effectiveness per age group from statistical analysis that used the total number of cases across various outbreaks rather than transmission dynamics. We did not identify any study estimating waning rate of measles vaccine from recent measles case dynamics.
Added value of this study
Our study uses measles case data from England, reported between 2010 and 2020. We show that the transmission dynamics in that time period was consistent with a waning of vaccine-induced immunity, making infection in young adults more common. We estimated that transmission from vaccinated cases was only slightly less common than transmission from unvaccinated cases. The increase in vaccinated cases and transmission from vaccinated cases increased the burden of measles in near-elimination settings.
Implications of all the available evidence
Our study shows that measles cases caused by waning of immunity are becoming more common. As the proportion of the overall population vaccinated against measles increases, and vaccine coverage dropped in many countries near elimination between 2020 and 2022, large outbreaks become more likely. Close monitoring of double-vaccinated cases is needed to assess their ability to cause onward transmission.
