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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Miyazaki, A; Kandasamy, S; Michael, H; Langel, SN; Paim, FC; Chepngeno, J; Alhamo, MA; Fischer, DD; Huang, H-C; Srivastava, V; Kathayat, D; Deblais, L; Rajashekara, G; Saif, LJ; Vlasova, AN

Published Date

  • October 8, 2018

Published In

Volume / Issue

  • 36 / 42

Start / End Page

  • 6270 - 6281

PubMed ID

  • 30219368

Pubmed Central ID

  • PMC6180620

Electronic International Standard Serial Number (EISSN)

  • 1873-2518

Digital Object Identifier (DOI)

  • 10.1016/j.vaccine.2018.09.008


  • eng

Conference Location

  • Netherlands