Escherichia coli Nissle 1917 Enhances Efficacy of Oral Attenuated Human Rotavirus Vaccine in a Gnotobiotic Piglet Model.

Husheem Michael,Anastasia N Vlasova,David D Fischer,Ayako Miyazaki,Maryssa K Kick,Juliet Chepngeno,Joshua O Amimo,Francine C Paim,Gireesh Rajashekara,Linda J Saif,Stephanie N Langel

doi:10.3390/vaccines10010083

Husheem Michael, Anastasia N Vlasova + Show 9 more

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https://doi.org/10.3390/vaccines10010083

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Abstract

Human rotavirus (HRV) infection is a major cause of viral gastroenteritis in young children worldwide. Current oral vaccines perform poorly in developing countries where efficacious vaccines are needed the most. Therefore, an alternative affordable strategy to enhance efficacy of the current RV vaccines is necessary. This study evaluated the effects of colonization of neonatal gnotobiotic (Gn) pigs with Escherichia coli Nissle (EcN) 1917 and Lacticaseibacillus rhamnosus GG (LGG) probiotics on immunogenicity and protective efficacy of oral attenuated (Att) HRV vaccine. EcN-colonized pigs had reduced virulent HRV (VirHRV) shedding and decreased diarrhea severity compared with the LGG-colonized group. They also had enhanced HRV-specific IgA antibody titers in serum and antibody secreting cell numbers in tissues pre/post VirHRV challenge, HRV-specific IgA antibody titers in intestinal contents, and B-cell subpopulations in tissues post VirHRV challenge. EcN colonization also enhanced T-cell immune response, promoted dendritic cells and NK cell function, reduced production of proinflammatory cytokines/Toll like receptor (TLR), and increased production of immunoregulatory cytokines/TLR expression in various tissues pre/post VirHRV challenge. Thus, EcN probiotic adjuvant with AttHRV vaccine enhances the immunogenicity and protective efficacy of AttHRV to a greater extent than LGG and it can be used as a safe and economical oral vaccine adjuvant.

Highlights

Human rotavirus (HRV) is the leading cause of viral gastroenteritis in infants and children that results in significant morbidity and mortality, especially in developing countries [1,2,3]
Our results demonstrated that the probiotic Escherichia coli Nissle (EcN) increased efficacy of oral attenuated HRV (AttHRV) vaccine by increasing both innate and adaptive immune responses to protect against virulent HRV (VirHRV) challenge
Using the relevant neonatal piglet model of HRV pathogenesis, we previously demonstrated the impact of two probiotics (EcN (Gram-negative probiotic) and Lacticaseibacillus rhamnosus GG (LGG) (Gram-positive probiotic)) on immune responses following VirHRV challenge; in this study we determined the impacts of these probiotics on innate and adaptive immune responses following oral 2× AttHRV vaccination and pre/post VirHRV challenge

Summary

Introduction

Human rotavirus (HRV) is the leading cause of viral gastroenteritis in infants and children that results in significant morbidity and mortality, especially in developing countries [1,2,3]. Studies have shown that there is reduced efficacy of HRV and other vaccines in developing countries, which presents a major concern and a global health challenge [4,5,6,7]. Early colonization by probiotic species may promote gut immunity maturation to enhance oral vaccine efficacy and moderate the severity of enteric infections. Previous studies demonstrated that colonization of Gn piglets with LGG and Bifidobacterium lactis resulted in a significant reduction in both fecal HRV shedding titers and diarrhea severity in the Gn piglet model of HRV infection [12]

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