Abstract
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.
Highlights
Human rotavirus (HRV) is a leading cause of diarrhea in children
These findings indicate that malnourished pigs generated lower HRV-specific antibody responses in serum and small intestinal contents post-virulent HRV (VirHRV) challenge
In contrast sufficient diet pigs generated significantly increased IgA antibody responses to the attenuated HRV (AttHRV) vaccination, reflected by increased B cell memory IgA antibody responses in serum and small intestinal contents post-VirHRV challenge, and protection against VirHRV challenge that was associated with decreased viral shedding and diarrhea (Table 1) [17]
Summary
Human rotavirus (HRV) is a leading cause of diarrhea in children. It causes significant morbidity and mortality, especially in developing countries [1]. The efficacy of RV vaccines is low in developing compared with developed countries [2]. Malnutrition is a major contributor to the high mortality from viral gastroenteritis in low socio-economic status countries [6,7,8]. Some clinical studies have reported decreased protection rates against RV diarrhea following RV vaccination of malnourished children [9, 10]. Studies to elucidate the effect of malnutrition on B cell responses following oral HRV vaccine are lacking
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