Long-term waning of vaccine-induced immunity to measles in England: a mathematical modelling study.

Abstract

Background: Among people infected with measles in England between 2010 and 2019, the proportion of cases who had previously received two doses of vaccine has increased, especially among young adults. Possible explanations include rare infections in vaccinated individuals who did not gain immunity upon vaccination, made more common because fewer individuals in the population were born in the endemic era, before vaccination was introduced, and exposed as part of endemic transmission, or the waning of vaccine-induced immunity, which would present new challenges for measles control in near-elimination settings. We aimed to evaluate whether measles dynamics observed in England between 2010 and 2019 were in line with a waning of vaccine-induced immunity.

Methods: We used a compartmental mathematical model stratified by age group, region, and vaccine status, fitted to individual-level case data reported in England from 2010 to 2019 and collected by the UK Health Security Agency. The deterministic model was fitted using Monte Carlo Markov Chains under three scenarios: without the waning of vaccine-induced immunity, with waning depending on time since vaccination, and with waning depending on time since vaccination, starting in 2000. We generated stochastic simulations from the fitted parameter sets to evaluate which scenarios could replicate the transmission dynamics observed in vaccinated cases in England.

Findings: The scenario without waning overestimated the number of one-dose recipients among measles cases, and underestimated the number of two-dose recipients among cases older than 15 years (median 75 cases [95% simulation interval (SI) 44-124] in simulations without waning, 196 [95% SI 122-315] in simulations when waning was included, 188 [95% SI 118-301] in simulations when waning started in 2000, and 202 observed cases). The number of onward transmissions from vaccinated cases was 83% (95% credible interval 72-91%) of the number of transmissions from unvaccinated cases. The estimated waning rate was slow (0·039% per year of age; 95% credible interval 0·034-0·044% per year in the best-fitting scenario with waning starting in 2000), but sufficient to increase measles burden.

Interpretation: Measles case dynamics in England are consistent with scenarios assuming the waning of vaccine-induced immunity. Since measles is highly infectious, slow waning leads to a heightened burden in outbreaks, increasing the number of measles cases in people who are both vaccinated and unvaccinated. Our findings show that although the vaccine remains highly protective against measles infections for decades and most transmission is connected to people who are unvaccinated, breakthrough infections are increasingly frequent for individuals aged 15 years and older who have been vaccinated twice.

Funding: National Institute for Health and Care Research and Wellcome Trust.