Key result
In a neonatal gnotobiotic pig model, a deficient diet impaired B cell mucosal and systemic immune responses following HRV vaccination and challenge, decreasing the protective efficacy of the vaccine.
Why the study?
Malnutrition is prevalent in developing countries and may contribute to decreased oral human rotavirus vaccine efficacy, posing a global health concern.
Does a deficient diet (malnutrition) impair the efficacy and B cell immune responses of an oral attenuated human rotavirus vaccine in a gnotobiotic pig model?
Does a deficient diet (malnutrition) impair the efficacy and B cell immune responses of an oral attenuated human rotavirus vaccine in a gnotobiotic pig model?
Malnutrition impairs mucosal and systemic B cell immune responses to oral rotavirus vaccination and subsequent challenge in a gnotobiotic pig model, suggesting a mechanism for reduced vaccine effectiveness in developing countries.
Malnutrition may compromise HRV vaccine efficacy in neonates; leaves open B-cell mechanisms and human translation.
Human rotavirus (HRV) is a leading cause of morbidity and mortality in children, especially in developing countries. Malnutrition is prevalent in these countries, which may contribute to the decreased oral vaccine efficacy, posing a concern for global health. Neonatal gnotobiotic (Gn) pigs closely resemble human infants in their anatomy, physiology, and outbred status and are a unique model to investigate malnutrition, oral live attenuated HRV (AttHRV) vaccination, and subsequent virulent HRV (VirHRV) challenge. We evaluated the impact of malnutrition on AttHRV vaccine efficacy and B cell immune responses in neonatal germfree (GF) or Gn pigs transplanted with human infant fecal microbiota (HIFM). Pigs were fed either deficient or sufficient bovine milk diets. Malnutrition did not significantly affect the serum and intestinal contents total or HRV-specific IgG and IgA antibody titers pre VirHRV challenge. However, HRV-specific IgG and IgA antibody secreting cells (ASCs) were reduced in blood or intestinal tissues following AttHRV vaccination and pre VirHRV challenge in deficient HIFM transplanted pigs. Furthermore, post-VirHRV challenge, deficient HIFM pigs had decreased total Ig and HRV-specific IgG and IgA antibody titers in serum or intestinal contents, in addition to decreased HRV-specific IgG and IgA ASCs in blood and ileum, compared with sufficient HIFM pigs. Our results indicate that deficient diet impairs B cell mucosal, and systemic immune responses following HRV vaccination, and challenge. The impaired immune responses contributed to the decreased protective efficacy of the AttHRV vaccine, suggesting that malnutrition may significantly reduce the effectiveness of oral HRV vaccines in children in developing countries.
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Michael et al. (2020) studied Human rotavirus (HRV) vaccination efficacy and malnutrition. Deficient bovine milk diet (malnutrition) vs. Sufficient bovine milk diet was evaluated on HRV-specific IgG and IgA antibody secreting cells (ASCs) and antibody titers. In a neonatal gnotobiotic pig model, a deficient diet impaired B cell mucosal and systemic immune responses following HRV vaccination and challenge, decreasing the protective efficacy of the vaccine.
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