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

Abstract

Background/ObjectivesLive 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 act as an immune adjuvant to increase rates of seroconversion after LAIV administration.Subjects/MethodsWe conducted a randomized double-blind placebo-controlled pilot study to determine if LGG improved rates of seroconversion after administration of LAIV. We studied 42 healthy adults during the 2007–8 influenza season. All subjects received LAIV and then were randomized to LGG or placebo twice daily for 28 days. HAI titers were assessed at baseline, day 28, and day 56 to determine rates of seroconversion. Subjects were assessed for adverse events throughout the study period.Results39 subjects completed the per protocol analysis. Both LGG and LAIV were well tolerated. Protection rates against the vaccine H1N1 and B strains was similar 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% CI 1.04–3.22, P=0.048).ConclusionLactobacillus GG is potential as an important adjuvant to improve influenza vaccine immunogenicity. Future studies of probiotics as immune adjuvants may need to consider specifically examining vaccine naïve or seronegative subjects, target mucosal immune responses, or focus on groups known to have poor response to influenza vaccines.

Selection of Adjuvants for Enhanced Vaccine Potency

“…Lactobacillus GG has been shown to have certain adjuvantation effect for live-attenuated flu vaccine in healthy adults [397]. Gram-positive enhancer matrix (GEM) particles derived from Lactococcus lactis was effective for intranasal vaccination with subunit flu vaccine in mice [398].…”

Probiotics, antibiotics and the immune responses to vaccines

“…( p ¼ 0.048), but not to the H1N1 or B strain no effect on seroconversion at day 56 [90] rstb.royalsocietypublishing.org Phil. Trans.…”

Probiotics and Bacterial Immunomodulators for Prevention of Respiratory Infections

“…Вместе с тем получены интересные сведения о влиянии лактобактерий на эффективность вакцинации против гриппа. Например, в двойном слепом плацебоконтролируемом исследова-нии, проведенном на 42 здоровых взрослых, было пока-зано, что прием Lactobacillus GG в течение 28 сут после вакцинации способствовал нарастанию более высоко-го титра защитных антител по сравнению с группой, получавшей только противогриппозную вакцину [10]. Аналогичные результаты продемонстрированы и другими исследователями [11][12][13][14].…”