Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial

L E Davidson, A-M Fiorino, D R Snydman, P L Hibberd, L E Davidson, A-M Fiorino, D R Snydman, P L Hibberd

Abstract

Background/objectives: 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.

Subjects/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).

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00620412.

Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflict of interest.

Please note that the Laboratory for Specialized Clinical Studies located at the Cincinnati Children’s Hospital Medical Center was contracted to run the HAI assays on the sera. The lab was blinded to the treatment and vaccine given to study subjects. This lab does contract work with a number of sponsors, but has no conflicts of interest and received no financial gain due to the results of this study.

© 2011 Macmillan Publishers Limited All rights reserved

Figures

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Figure 1
Participant Flow Diagram

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