Vitamin A deficiency impairs the immune response to intranasal vaccination and RSV infection in neonatal calves

Authors: MCGILL, JODI - Iowa State University; KELLY, SEAN - Iowa State University; GUERRA-MAUPOME, MARIANA - Iowa State University; WINKLEY, EMMA - Kansas State University; HENNINGSON, JAMIE - Kansas State University; NARASIMHAN, BALAJI - Iowa State University; Sacco, Randy

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/3/2019
Publication Date: 10/22/2019
Citation: McGill, J.L., Kelly, S.M., Guerra-Maupome, M., Winkley, E., Henningson, J., Narasimhan, B., Sacco, R.E. 2019. Vitamin A deficiency impairs the immune response to intranasal vaccination and RSV infection in neonatal calves. Scientific Reports. 9(15157). https://doi.org/10.1038/s41598-019-51684-x.
DOI: https://doi.org/10.1038/s41598-019-51684-x

Interpretive Summary: Vitamin A deficiency is one of the most prevalent nutrition-related health problems in the world and a significant factor in the risk of developing respiratory infections. Respiratory syncytial virus (RSV) is a leading cause of respiratory infections in human infants and calves. In this study, we examined the impact of vitamin A deficiency on the response to vaccination and infection with bovine RSV. Two groups of calves were fed milk replacers that had different amounts of vitamin A. One group of calves was fed a milk replacer with sufficent vitamin A and the other group was fed a milk replacer deficient in vitamin A. These two groups of calves were then split into two groups, one received a novel RSV vaccine and the other group no vaccine. All four groups of calves were then infected with bovine respiratory syncytial virus (bRSV). Our results show that vitamin A deficient calves are unable to respond to the vaccine and are provided no protection against later infection with bRSV. Our results suggest that particular care should be taken in managing nutrition of infants and calves to avoid vitamin A deficiency.

Technical 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 respiratory syncytial virus (BRSV) is a primary cause of lower respiratory tract disease in young cattle. The calf model of BRSV infection is useful to model the immune response to human RSV infection. We have previously developed an amphiphilic polyanhydride nanoparticle (NP) 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 and are afforded no protection from BRSV challenge. VAD animals have significant abnormalities in the inflammatory response in the infected lung, including dysregulated expression of IL-6, IFN gamma and IL-13, but reduced IL-17 expression. 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.