Short- and long-term impact of vaccination against cytomegalovirus: a modeling study

Figures

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  Fig. 1. Schematic of the transmission model. Shown are epidemiological transitions in the transmission model without vaccination. Seronegative persons (susceptible, S) acquire primary infection (I1) either vertically from their seropositive mothers (with probability q) or horizontally (with the force of infection λ) via contact with acutely infected persons in three infectious classes (I1, I2, I3). After primary infection (duration 1/γ year), persons become latently infected with low antibody concentrations (latent, L). In this class, re-infection occurs at a rate zλ, where z is the reduction in susceptibility to re-infection in latently infected persons compared to seronegative persons, and reactivation occurs at a rate ρ. After reactivation/re-infection (duration 1/γ year), persons transit to the latent class with high antibody concentrations (boosted, B) with probability pLB, where further re-infection and reactivation events can occur (I3). Note that vertical transmission from mother to child includes both congenital and postnatal transmission via breastfeeding. The population is stratified by sex and age, and the forces of infection and reactivation rates are age- and sex-specific…

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  Fig. 2. Overview of the estimation results. a, b The estimated age-specific prevalence of seronegative persons, seropositive persons with low antibody concentrations, and seropositive persons with high antibody concentrations in females (a) and males (b), respectively. c The age-specific reactivation rates per year for females (black) and males (blue), respectively. The solid lines represent the estimated medians, and the shaded regions correspond to 95% credible intervals obtained from 1000 parameter samples from the posterior distribution. The circles are seroprevalence data [33] indicating the fraction of samples that would be classified as seronegative with the cut-off specified by the supplier of the assay. The circle size gives a measure for the number of samples in 1-year age groups. The number of samples per 1-year age group is approximately 35 (females) and 30 (males). Note that the seroprevalence is estimated with high precision and that credible intervals for the reactivation rates are broad

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  Fig. 3. Universal vaccination of females with a vaccine preventing (re-)infection and reactivation. a The incidence of cCMV. b The incidence of primary infections and re-infections/reactivations during the first 50 years after the start of vaccination of 25-year-old women. The proportion of effectively vaccinated women (vaccination coverage × vaccine efficacy) is 70%, and the duration of protection is 10 years. c The reduction in cCMV after 20 years for different vaccination ages (10, 25, and 50 years) and proportions of effectively vaccinated women

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  Fig. 4. Elimination and persistence for universal vaccination with a vaccine preventing (re-)infection and reactivation. CMV elimination is feasible for effectively vaccinated proportions and durations of protection above the curve, while below the curve CMV cannot be eliminated. The curves correspond to the effective reproduction number equal to 1. The parameter values used in Table 1 are depicted as the black circle (70% and 10 years). For all vaccination strategies, the longer the duration of protection, the smaller proportion of persons would need to be effectively vaccinated to eliminate CMV. Vaccination of females only at the age of 10 or 25 years would require a vaccine with a longer duration of protection for elimination than vaccination of both males and females at the age of 6 months or at 10 years (e.g., about 27 years vs 20 years if 60% of the target group are effectively vaccinated)