A randomized controlled trial to evaluate the effect of influenza vaccination and probiotic supplementation on immune response and incidence of influenza-like illness in an elderly population in Indonesia

Abstract

Aim To investigate the effect of influenza vaccination with or without probiotic supplementation on the immune response and incidence of influenza-like illness (ILI) in the elderly. Methods A randomized double-blind, placebo-controlled trial with a modified factorial design was conducted in 554 healthy elderly subjects aged 67 ± 5.6 (ranging from 60–90) years old in the Primary Health Care Center (Puskesmas area) of the Pulo Gadung District East Jakarta. Subjects received either a trivalent influenza vaccine or placebo at the start of the study, and a probiotic supplement (Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011) or a placebo for 6 months. Subjects were randomly assigned into four intervention groups: influenza vaccine and probiotics (n = 141), influenza vaccine and placebo (n = 136), placebo and probiotics (n = 140), and both placebo (n = 137). The primary outcome was ILI incidence within 6 months. The secondary outcomes were seroprotection and seroconversion rates at 1, 4, and 6 months after administering the interventions. Results This study showed that the trivalent influenza vaccine increased seroprotection (RR 3.6 [95%CI 2.92–4.47]; p<0.010) and seroconversion (RR 29.8 [95%CI 11.1–79.5]; p<0.010) rates 1 month after vaccination in elderly people while the probiotic supplement did not alter influenza antibody titers (p = 1.000 and p = 0.210). The relative ILI incidence risk was similar between vaccinated and non-vaccinated groups, as well as in the probiotic group compared to the non-probiotic group. Conclusion The tested trivalent influenza vaccine significantly induced seroprotection and seroconversion in the vaccinated subjects, while probiotics administration did not influence these parameters. Vaccinated individuals displayed a similarly low ILI incidence as those in the Control Group. However, the observed trend towards a reduction of ILI incidence with probiotics supplementation warrants further assessments in a larger, at-risk population. Clinical trial registry number NCT03695432.

Novel Fermentates Can Enhance Key Immune Responses Associated with Viral Immunity

“…It has previously been demonstrated that an isolated acidic polysaccharide from the fungus Cordyceps militaris enhanced mRNA expression of IL-1β, IL-6, IL-10, and TNF-α, increased NO production and induced iNOS mRNA and protein expression in RAW 264.7 macrophage cells, as well as increasing TNF-α and IFN-γ in mice, to decrease virus titres in the bronchoalveolar lavage fluid and the lung of mice infected with influenza A virus to increase survival rate [17]. Similarly a studying involving Lactobacillus helveticus has been found to show a trending decrease in influenza like illness in an elderly population, warranting further investigation in at risk populations, this suggesting a similar role for both SC232, and SC234 [18]. Another study showed that germinated Rhynchosia nulubilis fermented with Pediococcus pentosaceus SC11, isolated from a salted small octopus, has immune-enhancing and anti-viral effects, inhibiting 3CL protease activity in SARS-CoV in immunocompromised mice, increased T lymphocyte production and spleenocyte proliferation, increased phagocytic activity, NO production via induction of iNOS, mRNA expression of IFN-γ, IFN-α and ISG15 in RAW 264.7 macrophage, and subsequent increase in expression of TNF-α [19], suggesting the role of GRC-SC11 in immunosuppressed patients for the support against SARS-CoV.…”

Novel Fermentates Can Enhance Key Immune Responses Associated with Viral Immunity

“…It has previously been demonstrated that an isolated acidic polysaccharide from the fungus Cordyceps militaris enhanced mRNA expression of IL-1β, IL-6, IL-10, and TNF-α, increased NO production, and induced iNOS mRNA and protein expression in RAW 264.7 macrophage cells, as well as increasing TNF-α and IFN-γ in mice, to decrease virus titres in the bronchoalveolar lavage fluid and the lungs of mice infected with influenza A virus to increase survival rate [ 18 ]. Similarly, a study involving Lactobacillus helveticus has showed a trending decrease in influenza-like illness in an elderly population, suggesting it could elicit a similar effect [ 19 ]. Another study showed that germinated Rhynchosia nulubilis fermented with Pediococcus pentosaceus SC11 has immune-enhancing and anti-viral effects, inhibiting 3CL protease activity in SARS-CoV in immunocompromised mice, increased T lymphocyte production and splenocyte proliferation, increased phagocytic activity, NO production via induction of iNOS, mRNA expression of IFN-γ, IFN-α, and ISG15 in RAW 264.7 macrophages, and subsequent increase in the expression of TNF-α [ 20 ], suggesting the role of GRC-SC11 in immunosuppressed patients for support against SARS-CoV.…”

Accounting for the health risk of probiotics

“…Likewise, a clinical trial that examined the effects of probiotic vaccination on the immune response and the incidence of influenza-like diseases in elderly people, did not show any changes in the level of influenza antibody. The relative risk of the influenza-like diseases in vaccinated, non-vaccinated, and probiotic groups was also similar [ 74 ]. Crucially, results from other clinical studies indicated that probiotics consumption could even raise the chance of developing autoimmune disorders.…”