Protein deficiency reduces efficacy of oral attenuated human rotavirus vaccine in a human infant fecal microbiota transplanted gnotobiotic pig model.

Abstract

BACKGROUND:

Low efficacy of rotavirus (RV) vaccines in developing African and Asian countries, where malnutrition is prevalent, remains a major concern and a challenge for global health.

METHODS:

To understand the effects of protein malnutrition on RV vaccine efficacy, we elucidated the innate, T cell and cytokine immune responses to attenuated human RV (AttHRV) vaccine and virulent human RV (VirHRV) challenge in germ-free (GF) pigs or human infant fecal microbiota (HIFM) transplanted gnotobiotic (Gn) pigs fed protein-deficient or -sufficient bovine milk diets. We also analyzed serum levels of tryptophan (TRP), a predictor of malnutrition, and kynurenine (KYN).

RESULTS:

Protein-deficient pigs vaccinated with oral AttHRV vaccine had lower protection rates against diarrhea post-VirHRV challenge and significantly increased fecal virus shedding titers (HIFM transplanted but not GF pigs) compared with their protein-sufficient counterparts. Reduced vaccine efficacy in protein-deficient pigs coincided with altered serum IFN-α, TNF-α, IL-12 and IFN-γ responses to oral AttHRV vaccine and the suppression of multiple innate immune parameters and HRV-specific IFN-γ producing T cells post-challenge. In protein-deficient HIFM transplanted pigs, decreased serum KYN, but not TRP levels were observed throughout the experiment, suggesting an association between the altered TRP metabolism and immune responses.

CONCLUSION:

Collectively, our findings confirm the negative effects of protein deficiency, which were exacerbated in the HIFM transplanted pigs, on innate, T cell and cytokine immune responses to HRV and on vaccine efficacy, as well as on TRP-KYN metabolism.

• Authors: Ayako Miyazaki, Sukumar Kandasamy, Husheem Michael, Stephanie N Langel, Francine C Paim, Juliet Chepngeno, Moyasar A Alhamo, David D Fischer, Huang-Chi Huang, Vishal Srivastava, Dipak Kathayat, Loic Deblais, Gireesh Rajashekara, Linda J Saif, Anastasia N Vlasova
• Journal: Vaccine (Vaccine) Vol. 36 Issue 42 Pg. 6270-6281 (10 08 2018) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 30219368 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Rotavirus Vaccines
• Vaccines, Attenuated
• Tryptophan

Topics

• Animals
• Feces (microbiology)
• Germ-Free Life
• Humans
• Infant
• Microbiota (immunology)
• Protein Deficiency (complications, immunology, metabolism)
• Rotavirus (immunology, pathogenicity)
• Rotavirus Vaccines (therapeutic use)
• Swine
• Tryptophan (metabolism)
• Vaccines, Attenuated (therapeutic use)