Abstract

Respiratory syncytial virus (RSV) infection is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide. Vitamin A deficiency (VAD) is one of the most prevalent nutrition-related health problems in the world and is a significant risk factor in the development of severe respiratory infections in infants and young children. Bovine RSV (BRSV) is a primary cause of lower respiratory tract disease in young cattle. The calf model of BRSV infection is useful to understand the immune response to human RSV infection. We have previously developed an amphiphilic polyanhydride nanoparticle (NP)-based vaccine (i.e., nanovaccine) encapsulating the fusion and attachment proteins from BRSV (BRSV-NP). Calves receiving a single, intranasal dose of the BRSV-NP vaccine are partially protected from BRSV challenge. Here, we evaluated the impact of VAD on the immune response to the BRSV-NP vaccine and subsequent challenge with BRSV. Our results show that VAD calves are unable to respond to the mucosal BRSV-NP vaccine, are afforded no protection from BRSV challenge and have significant abnormalities in the inflammatory response in the infected lung. We further show that acute BRSV infection negatively impacts serum and liver retinol, rendering even well-nourished individuals susceptible to VAD. Our results support the use of the calf model for elucidating the impact of nutritional status on mucosal immunity and respiratory viral infection in infants and underline the importance of VA in regulating immunity in the respiratory mucosa.

Highlights

  • Respiratory syncytial virus (RSV) infection is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide

  • Vitamin A deficiency (VAD) is endemic in the geographical regions which are hit hardest by RSV1, and is highly prevalent in premature infants, a population known to be at increased risk from RSV7,8

  • RSV infection is most severe in premature infants, neonates and young children; and complications from RSV infection are most prevalent in developing countries[21,23]

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Summary

Introduction

Respiratory syncytial virus (RSV) infection is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide. Vitamin A deficiency (VAD) is one of the most prevalent nutrition-related health problems in the world and is a significant risk factor in the development of severe respiratory infections in infants and young children. Human respiratory syncytial virus (RSV) is a leading cause of severe acute lower respiratory tract disease in infants and young children worldwide[20,21] and accounts for up to 70% of hospitalized bronchiolitis cases in industrialized countries[22]. Bovine respiratory syncytial virus (BRSV) is closely related to human RSV and is a primary cause of severe acute lower respiratory tract disease in young cattle. The calf model is useful to understand the immune response to RSV infection because it is a physiologic host-pathogen interaction, represents a tractable model of the infant immune system, and is a scalable model which can be used to test novel therapeutics and intervention strategies

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