Author:
McGill Jodi L.,Kelly Sean M.,Guerra-Maupome Mariana,Winkley Emma,Henningson Jamie,Narasimhan Balaji,Sacco Randy E.
Abstract
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.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
Publisher
Springer Science and Business Media LLC
Reference65 articles.
1. World Health Organization. Global prevalence of vitamin A deficiency in populations at risk 1995-2005: WHO global database on vitamin A deficiency. (World Health Organization, 2009).
2. Rahman, M. M. et al. Simultaneous vitamin A administration at routine immunization contact enhances antibody response to diphtheria vaccine in infants younger than six months. J Nutr 129, 2192–2195 (1999).
3. Bhaskaram, P. & Rao, K. V. Enhancement in seroconversion to measles vaccine with simultaneous administration of vitamin A in 9-months-old Indian infants. Indian J Pediatr 64, 503–509 (1997).
4. Timoneda, J. et al. Vitamin A Deficiency and the Lung. Nutrients 10,
https://doi.org/10.3390/nu10091132
(2018).
5. Stephens, D., Jackson, P. L. & Gutierrez, Y. Subclinical vitamin A deficiency: a potentially unrecognized problem in the United States. Pediatr Nurs 22(377–389), 456 (1996).
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