Research ArticleEpidemiology

Vaccine waning and mumps re-emergence in the United States

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Science Translational Medicine  21 Mar 2018:
Vol. 10, Issue 433, eaao5945
DOI: 10.1126/scitranslmed.aao5945
  • Fig. 1 Synthesis of prospective and retrospective cohort studies estimating the relative risk of clinical mumps in vaccinated and unvaccinated individuals.

    We illustrate the results of our meta-analysis of studies of mumps vaccine effectiveness, from which we estimated rates of vaccine waning. (A) Shown here is how estimates of vaccine effectiveness (defined as one minus the relative risk (RR) of experiencing mumps for a vaccinated individual, relative to an unvaccinated individual) differ across the six studies analyzed here. Time since last dose accounts for 66.4% of residual variation in estimates after accounting for random sources of between-study heterogeneity. Points representing study-level estimates are scaled in size to reflect differences in sample size. Lines signify 95% confidence intervals (CIs); arrows indicate where values rounded to the nearest hundredth equal zero. (B) At 6 months after vaccine receipt (the earliest time point assessed in primary studies), we estimate that 96.4% (94.0 to 97.8%) of recipients are protected; we apply this as our estimate of the probability of vaccine take. (C) A parsimonious model of exponentially distributed durations of protection predicts loss of protection after, on average, Embedded Image years (95% CI, 16.7 to 51.1), as indicated by the yellow-plotted area. The blue-plotted area illustrates the distribution of times to loss of protection for vaccinated individuals, generated by pooling exponential distributions parameterized using estimates of ωV. (D) Contrary to the hypothesis of reduced effectiveness against diverse mumps genotypes currently in circulation, we did not identify evidence of a decline in vaccine effectiveness over time, whereas evidence of waning vaccine-derived immunity persisted in a model adjusting for calendar year. Unadjusted estimates of the relative risk of clinical mumps given vaccination—and estimates adjusted for time since vaccination, years since 1964, and doses received—are calculated via meta-regression using incidence data from the original studies (13, 4650). (E) Using this meta-regression framework, we identified no difference (posterior two-sided P > 0.1) in the waning rate (as defined by the inverse of the association between time since vaccination and relative risk of mumps given vaccination; see Materials and Methods) after receipt of a first or second dose (95% CI, 33% decrease to 72% increase in the relative risk of mumps given vaccination per log year since vaccination; posterior two-sided P > 0.1).

  • Fig. 2 Mumps incidence and estimates of population susceptibility over time.

    Here, we illustrate changes in the proportion of the population, by age, predicted to be susceptible to mumps on the basis of the estimated waning rate of vaccine-derived immune protection and the incidence of mumps infection in the population. (A) Overall rates of reported cases declined after vaccine licensure in 1967, punctuated by outbreaks primarily among adolescents from 1984 to 1992 and recent outbreaks (2006 onward) centered among young adults. These outbreaks have corresponded with (B) peaks in the model-inferred proportion of individuals susceptible to mumps infection at 10 to 19 and 20 to 29 years of age, respectively, and (C) reductions in the proportion of infections that cause symptoms and are reported because of vaccine protection against symptoms. (D) Changes in the proportion of individuals susceptible to infection across different ages are plotted against rates of reported cases.

  • Fig. 3 Anticipated transmission dynamics under scenarios of vaccine escape and vaccine waning.

    Here, we use a stochastic simulation model to predict the epidemiology of mumps outbreaks under the scenario of mumps virus escaping vaccine-induced immune pressure and the scenario of waning vaccine-derived immunity. (A) A stochastic model of an emerging vaccine-escape strain of mumps virus in a vaccinated population predicts excess incidence in young age groups, in keeping with their higher historical burden of mumps. (B) In contrast, the fit of a model incorporating waning vaccine-derived immunity matches the observed age distribution. (C) Higher overall incidence rates and (D) a younger age distribution of cases are predicted when immune responses to the vaccine offer minimal cross-protection against the circulating strain, as compared to the fit of the model with waning vaccine immunity. (E) Whereas the model with a viral-escape (VE) strain can reproduce the age distribution of cases at low degrees of immunological mismatch, (F) lower-than-reported incidence is expected under this scenario, again in contrast to the fit of a model with waning vaccine immunity. Lines in (E) and (F) signify 95% CIs.

  • Fig. 4 Age-specific immunity and transmission dynamics under two- and three-dose vaccine schedules.

    Waning vaccine-derived protection in the population raises the question of how additional vaccine doses would affect mumps transmission. To address this question, we evaluated several scenarios. (A) Cohorts over 40 years of age as of 2016 were exposed to endemic transmission before and shortly after vaccine rollout and likely retain life-long protection. However, a population protected only by two-dose vaccination would be expected to experience high prevalence of susceptibility over 20 years of age. (B and C) Our modeling suggests that the duration of protection can be extended through young adulthood by adding a third dose around 18 years of age, whereas routine booster doses every 10 or 20 years would be expected to sustain longer-term protection. Lines and shaded areas delineate median estimates and 95% CIs, respectively. (D) Under transmission dynamics estimated as of 2016, protection in young adult age groups achieved through the use of a third vaccine dose is expected to reduce the effective reproductive number (RE) below 1. We, however, predict RE to approach 1.10 under the two-dose schedule as cohorts that experienced high rates of mumps infection age out of the population; larger reductions in RE are sustained at higher coverage and with more frequent dosing. Colors are the same as in (A) to (C). R0, basic reproductive number. (E) In turn, these extensions of protection provide a stronger barrier against emergence of strains escaping vaccine immunity. A new strain with 8.5% (95% CI, 7.6 to 9.8%) probability of evading vaccine-induced immunity and infecting a vaccine-protected individual would be expected to succeed under a three-dose schedule with low coverage. We, however, estimate that a new strain would require 22.9% (95% CI, 16.4 to 29.7%) probability of infecting such an individual to emerge in a population with 88% uptake of the third dose and 10-year boosters. Lines denote 95% CIs, and shaded areas represent distributions around RE estimates.

Supplementary Materials

  • www.sciencetranslationalmedicine.org/cgi/content/full/10/433/eaao5945/DC1

    Materials and Methods

    Fig. S1. Fitted endemic transmission dynamics before vaccine rollout.

    Fig. S2. Reductions in mumps notifications correspond with increases in vaccine coverage and a declining basic reproductive number.

    Fig. S3. Birth cohorts accounting for reported cases over time.

    Fig. S4. Changes in estimates of the susceptible population under scenarios of declining reporting.

    Fig. S5. Changes in estimates of R0 over time under scenarios of declining reporting.

    Fig. S6. Aggregated age-specific notification rates.

    Fig. S7. Estimates of population susceptibility and R0(t) under an assumption of time-invariant protection.

    Table S1. Studies included in meta-analysis assessing vaccine waning.

    Table S2. Model parameter definitions and values.

    References (5181)

  • Supplementary Material for:

    Vaccine waning and mumps re-emergence in the United States

    Joseph A. Lewnard* and Yonatan H. Grad*

    *Corresponding author. Email: jlewnard{at}hsph.harvard.edu (J.A.L.); ygrad{at}hsph.harvard.edu (Y.H.G.)

    Published 21 March 2018, Sci. Transl. Med. 10, eaao5945 (2018)
    DOI: 10.1126/scitranslmed.aao5945

    This PDF file includes:

    • Materials and Methods
    • Fig. S1. Fitted endemic transmission dynamics before vaccine rollout.
    • Fig. S2. Reductions in mumps notifications correspond with increases in vaccine coverage and a declining basic reproductive number.
    • Fig. S3. Birth cohorts accounting for reported cases over time.
    • Fig. S4. Changes in estimates of the susceptible population under scenarios of declining reporting.
    • Fig. S5. Changes in estimates of R0 over time under scenarios of declining reporting.
    • Fig. S6. Aggregated age-specific notification rates.
    • Fig. S7. Estimates of population susceptibility and R0(t) under an assumption of time-invariant protection.
    • Table S1. Studies included in meta-analysis assessing vaccine waning.
    • Table S2. Model parameter definitions and values.
    • References (4648, 50, 5581)

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