title: Predicting the relative impacts of maternal and neonatal respiratory syncytial virus (RSV) vaccine target product profiles: A consensus modelling approach.
abstract: Respiratory syncytial virus (RSV) is the major viral cause of infant and childhood lower respiratory tract disease worldwide. Defining the optimal target product profile (TPP) is complicated due to a wide range of possible vaccine properties, modalities and an incomplete understanding of the mechanism of natural immunity. We report consensus population level impact projections based on two mathematical models applied to a low income setting.
  
  
  
  Two structurally distinct age-specific deterministic compartmental models reflecting uncertainty associated with the natural history of infection and the mechanism by which immunity is acquired and lost were constructed. A wide range of vaccine TPPs were explored including dosing regime and uptake, and effects in the vaccinated individual on infectiousness, susceptibility, duration of protection, disease severity and interaction with maternal antibodies and natural induced immunity. These were combined with a range of vaccine implementation strategies, targeting the highest priority age group and calibrated using hospitalization data from Kilifi County Hospital, Kenya.
  
  
  
  Both models were able to reproduce the data. The impact predicted by the two models was qualitatively similar across the range of TPPs, although one model consistently predicted higher impact than the other. For a proposed realistic range of scenarios of TPP combinations, the models predicted up to 70% reduction in hospitalizations in children under five years old. Vaccine designs which reduced the duration and infectiousness of infection were predicted to have higher impacts. The models were sensitive to the coverage and rate of loss of vaccine protection but not to the interaction between vaccine and maternal/naturally acquired immunity.
  
  
  
  The results suggest that vaccine properties leading to reduced virus circulation by lessening the duration and infectiousness of infection upon challenge are of major importance in population RSV disease control. These features should be a focus for vaccine development.
authors.affiliation: Mathematical and Economics Modelling (MAEMOD) Research Group, Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Electronic address: pan@tropmedres.ac.
authors.forename: Wirichada
authors.initials: W
authors.lastname: Pan-Ngum
authors.affiliation: School of Mathematics, Alan Turing Building, University of Manchester, Oxford Road, Manchester, UK; KEMRI-Wellcome Trust Research Programme, KEMRI Centre for Geographic Medicine Research - Coast, Kilifi, Kenya.
authors.forename: Timothy
authors.initials: T
authors.lastname: Kinyanjui
authors.affiliation: KEMRI-Wellcome Trust Research Programme, KEMRI Centre for Geographic Medicine Research - Coast, Kilifi, Kenya.
authors.forename: Moses
authors.initials: M
authors.lastname: Kiti
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Taylor
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Toussaint
authors.affiliation: Mathematical and Economics Modelling (MAEMOD) Research Group, Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Sompob
authors.initials: S
authors.lastname: Saralamba
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Van Effelterre
authors.affiliation: KEMRI-Wellcome Trust Research Programme, KEMRI Centre for Geographic Medicine Research - Coast, Kilifi, Kenya; School of Life Sciences and WIDER, University of Warwick, Coventry, UK.
authors.forename: D James
authors.initials: DJ
authors.lastname: Nokes
authors.affiliation: Mathematical and Economics Modelling (MAEMOD) Research Group, Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: White
mesh_terms: D002675:Child, Preschool; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007630:Kenya / Q000453:epidemiology; D008297:Male; D008962:Models, Theoretical; D018357:Respiratory Syncytial Virus Infections / Q000453:epidemiology* / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D022261:Respiratory Syncytial Virus Vaccines
keywords: Contact pattern; Hospitalization; Kenya; RSV; Transmission model; Vaccine TPP