Effectiveness and efficiency of immunisation strategies to prevent RSV among infants and older adults in Germany: a modelling study

Abstract

Background: Recently, several novel RSV immunisation products that protect infants and older adults against RSV disease have been licensed in Europe. We estimated the effectiveness and efficiency of introducing these RSV immunisation strategies in Germany.

Methods: We used a Bayesian framework to fit a deterministic age-structured dynamic transmission model of RSV to sentinel surveillance and RSV-specific hospitalisation data in Germany from 2015 to 2019. The calibrated model was used to evaluate different RSV intervention strategies over 5 years: long-acting, single-dose monoclonal antibodies (mAbs) in high-risk infants aged 1-5 months; long-acting mAbs in all infants aged 1-5 months; seasonal vaccination of pregnant women and one-time seasonal vaccination of older adults (75 + /65 + /55 + years). We performed sensitivity analysis on vaccine uptake, seasonal vs. year-round maternal vaccination, and the effect of under-ascertainment for older adults.

Results: The model was able to match the various RSV datasets. Replacing the current short-acting mAB for high-risk infants with long-acting mAbs prevented 1.1% of RSV-specific hospitalisations in infants per year at the same uptake. Expanding the long-acting mAB programme to all infants prevented 39.3% of infant hospitalisations per year. Maternal vaccination required a larger number to be immunised to prevent one additional hospitalisation than a long-acting mAB for the same uptake. Vaccination of adults older than 75 years at an uptake of 40% in addition to Nirsevimab in all infants prevented an additional 4.5% of all RSV hospitalisations over 5 years, with substantial uncertainty in the correction for under-ascertainment of the RSV burden.

Conclusions: Immunisation has the potential to reduce the RSV disease burden in Germany.

Keywords: Immunisation; MAb; Mathematical modelling; RSV; Strategy.

Fig. 1

Model structure of RSV transmission and disease progression and mechanisms of immunisation

Fig. 2

Fitting results of the dynamic transmission model to the data using Bayesian inference. The plots show the median model prediction and the 95% posterior prediction intervals (PPI) (red ribbon or error bar) compared to data (black points). The model was fitted to German RSV-specific hospitalisation data (TK, A, B), German sentinel outpatient RSV cases (AGI, C, D), and seroconversion data from the Netherlands in < 1-year-olds (E)

Fig. 3

Forward-simulation results for the infant RSV immunisation strategies in Germany over five years compared to the base strategy (Palivizumab for high-risk infants). The panels show the overall average number of cases prevented (A), the percentage of cases prevented (B), and the number needed to vaccinate (NNV) (C). The numbers represent the prediction medians, the horizontal lines the 95% prediction interval

Fig. 4

Forward-simulation results for the single dose vaccination of older adults over 5 years in addition to Nirsevimab for all infants, compared to a base strategy of no adult vaccination (only Nirsevimab for all infants). The panels represent the annual average number of prevented symptomatic cases (A), the percentages prevented (B), and the corresponding numbers needed to vaccinate (C). The numbers represent the prediction medians, the horizontal lines represent the 95% prediction intervals. Under-ascertainment of adult RSV hospitalisations was accounted for by scaling the RSV-specific hospitalisations with two different scaling factors: 8 and 14 (purple/green)