title: Lactobacillus rhamnosus GG Dosage Affects the Adjuvanticity and Protection Against Rotavirus Diarrhea in Gnotobiotic Pigs.
abstract: OBJECTIVE
  The use of immunostimulatory strains of probiotics as adjuvants has been increasingly recognized as a promising approach in enhancing vaccine immunogenicity; however, dose effects of probiotic adjuvants are not well defined. In the present study, we examined dose effects of a commonly used probiotic strain, Lactobacillus rhamnosus GG (LGG), on immunomodulation with 2 different dosages.
  
  
  METHODS
  Neonatal gnotobiotic pigs were inoculated with 2 oral doses of attenuated human rotavirus (AttHRV) vaccines and fed with 5 doses (LGG5X; total 2.1 × 10(6) colony-forming units) or 9 doses (LGG9X; total 3.2 × 10(6) colony-forming units) of LGG, starting at 3 days of age.
  
  
  RESULTS
  Both LGG feeding regimens enhanced the protection rate of AttHRV vaccine against diarrhea on virulent human rotavirus challenge. LGG5X, but not LGG9X, significantly enhanced rotavirus-specific intestinal memory B-cell responses to AttHRV; LGG5X also significantly enhanced virus-specific intestinal immunoglobulin A (IgA) antibody-secreting cell responses. Both regimens significantly enhanced rotavirus-specific serum IgA antibody responses to AttHRV. They also enhanced rotavirus-specific interferon-γ-producing effector/memory T-cell responses to AttHRV vaccine, with LGG9X being more effective than LGG5X, and both regimens downregulated CD4+CD25-FoxP3+ regulatory T (Treg) cell responses in most lymphoid tissues examined prechallenge and postchallenge and maintained the CD4+CD25+FoxP3+ Treg population in the ileum and intraepithelial lymphocyte postchallenge. LGG9X, however, did not significantly reduce total CD4+CD25-FoxP3+ Treg frequencies in the intestine and transforming growth factor-β-producing and interleukin (IL)-10-producing Treg frequencies in the blood.
  
  
  CONCLUSIONS
  These results indicate that LGG at both dosages functioned as effective probiotic adjuvant for AttHRV vaccine, but different dosages differentially modulated immune responses to favor either the mucosal IgA response (LGG5X) or the T-cell response (LGG9X).
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg.
authors.forename: Ke
authors.initials: K
authors.lastname: Wen
authors.forename: Fangning
authors.initials: F
authors.lastname: Liu
authors.forename: Guohua
authors.initials: G
authors.lastname: Li
authors.forename: Muqun
authors.initials: M
authors.lastname: Bai
authors.forename: Jacob
authors.initials: J
authors.lastname: Kocher
authors.forename: Xingdong
authors.initials: X
authors.lastname: Yang
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wang
authors.forename: Sherrie
authors.initials: S
authors.lastname: Clark-Deener
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000187:drug effects; D003967:Diarrhea / Q000517:prevention & control* / Q000821:virology; D004305:Dose-Response Relationship, Drug; D005856:Germ-Free Life; D007070:Immunoglobulin A / Q000097:blood* / Q000276:immunology; D007422:Intestines / Q000276:immunology / Q000382:microbiology / Q000821:virology; D052201:Lacticaseibacillus rhamnosus; D019936:Probiotics / Q000008:administration & dosage*; D012401:Rotavirus / Q000276:immunology*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D013552:Swine; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
chemical_list: D007070:Immunoglobulin A; D022243:Rotavirus Vaccines