Vaccination strategies against respiratory syncytial virus

Abstract

Respiratory syncytial virus (RSV) is the most common cause of US infant hospitalization. Additionally, RSV is responsible for 10,000 deaths annually among the elderly across the United States, and accounts for nearly as many hospitalizations as influenza. Currently, several RSV vaccine candidates are under development to target different age groups. To evaluate the potential effectiveness of age-specific vaccination strategies in averting RSV incidence, we developed a transmission model that integrates data on daily infectious viral load and changes of behavior associated with RSV symptoms. Calibrating to RSV weekly incidence rates in Texas, California, Colorado, and Pennsylvania, we show that in all states considered, an infected child under 5 y of age is more than twice as likely as a person over 50 y of age to transmit the virus. Geographic variability in the effectiveness of a vaccination program across states arises from interplay between seasonality patterns, population demography, vaccination uptake, and vaccine mechanism of action. Regardless of these variabilities, our analysis showed that allocating vaccine to children under 5 y of age would be the most efficient strategy per dose to avert RSV in both children and adults. Furthermore, due to substantial indirect protection, the targeting of children is even predicted to reduce RSV in the elderly more than directly vaccinating the elderly themselves. Our results can help inform ongoing clinical trials and future recommendations on RSV vaccination.

Keywords: RSV; model; social contact; vaccination; viral load.

Fig. 1.

Structure and fit of the model. (A) Compartmental diagram of the transmission model. Individuals are born into a maternal immunity compartment M, and then transition to the first susceptible compartment S₁, where they can become infected I₁. Following infection, individuals transition to a recovered compartment R, where they are temporarily immune. Following waning, individuals transition to S₂, where they might be reinfected, but with milder infection I_2, which can be asymptomatic in adults. For clarity of depiction, age stratification is not displayed (SI Appendix). (B) Infectious viral load of the first infection and subsequent infections, as well as daily behavior changes during RSV infection (based on refs. 22, 25, 44). (C) Time series of recorded weekly RSV cases and model fit to California and Texas (model fit to Colorado and Pennsylvania is provided in SI Appendix, Fig. S4). (D) Data and model fit to the age distribution among RSV infections.

Fig. 2.

Age-specific average number of secondary infections generated per case. Each row identifies an age group that can be a source of infection. Each column identifies an age group that can be infected. The color at the intersection of the row and column indicates the number of secondary infections attributed to a single infective case. The average number of secondary cases from the source age group is tabulated in the rightmost column of each panel. California (A and B) and Texas (C and D) model predictions are shown for the entire RSV season (A and C) and for the first month of the RSV season (B and D). Similar trends are observed in Colorado and Pennsylvania (SI Appendix, Fig. S6).

Fig. 3.

Model predictions of RSV cases averted per vaccinated individual in California, Texas, Pennsylvania, and Colorado, assuming vaccine efficacies of 80% (A and B), 60% (C and D), and 40% (E and F). We assumed age-specific monthly vaccination coverages as observed for the influenza vaccine between 2010 and 2014. No reduction in viral load is imposed for vaccinated individuals who became infected. Cases averted are tallied for the two at-risk age groups: individuals younger than 5 y of age (A, C, and E) and individuals older than 50 y of age (B, D, and F).

Fig. 4.

Model predictions of proportion reduction in RSV cases in California, Texas, Pennsylvania, and Colorado, assuming vaccine efficacies of 80% (A and B), 60% (C and D), and 40% (E and F), respectively. We assumed age-specific monthly vaccination coverages as observed for the influenza vaccine between 2010 and 2014. No reduction in viral load was imposed on vaccinated individuals who became infected. Cases averted are tallied for the two at-risk age groups: individuals younger than 5 y of age (A, C, and E) and individuals 50 y of age or older (B, D, and F).