title: Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial.
abstract: OBJECTIVE
  Live-attenuated influenza vaccine (LAIV) protects against influenza by mucosal activation of the immune system. Studies in animals and adults have demonstrated that probiotics improve the immune response to mucosally delivered vaccines. We hypothesized that Lactobacillus GG (LGG) would function as an immune adjuvant to increase rates of seroconversion after LAIV administration.
  
  
  METHODS
  We conducted a randomized double-blind placebo-controlled pilot study to determine whether LGG improved rates of seroconversion after administration of LAIV. We studied 42 healthy adults during the 2007-2008 influenza season. All subjects received LAIV and then were randomized to LGG or placebo, twice daily for 28 days. Hemagglutinin inhibition titers were assessed at baseline, at day 28 and at day 56 to determine the rates of seroconversion. Subjects were assessed for adverse events throughout the study period.
  
  
  RESULTS
  A total of 39 subjects completed the per-protocol analysis. Both LGG and LAIV were well tolerated. Protection rates against the vaccine H1N1 and B strains were suboptimal in subjects receiving LGG and placebo. For the H3N2 strain, 84% receiving LGG vs 55% receiving placebo had a protective titer 28 days after vaccination (odds of having a protective titer was 1.84 95% confidence interval 1.04-3.22, P=0.048).
  
  
  CONCLUSIONS
  Lactobacillus GG is potential as an important adjuvant to improve influenza vaccine immunogenicity. Future studies of probiotics as immune adjuvants might need to specifically consider examining vaccine-naïve or sero-negative subjects, target mucosal immune responses or focus on groups known to have poor response to influenza vaccines.
authors.affiliation: Division of Geographic Medicine and Infectious Diseases, Department of Medicine, Tufts Medical Center, Boston, MA 02111, USA. ldavidson1@tuftsmedicalcenter.org
authors.forename: L E
authors.initials: LE
authors.lastname: Davidson
authors.forename: A-M
authors.initials: AM
authors.lastname: Fiorino
authors.forename: D R
authors.initials: DR
authors.lastname: Snydman
authors.forename: P L
authors.initials: PL
authors.lastname: Hibberd
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D007778:Lactobacillus / Q000276:immunology*; D008297:Male; D010865:Pilot Projects; D019936:Probiotics / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated