Protein deficiency reduces efficacy of oral attenuated human rotavirus vaccine in a human infant fecal microbiota transplanted gnotobiotic pig model.
Vaccine
; 36(42): 6270-6281, 2018 10 08.
Article
em En
| MEDLINE
| ID: mdl-30219368
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Deficiência de Proteína
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Vacinas Atenuadas
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Fezes
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Vida Livre de Germes
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Infant
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article