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.

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.
Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: NSB and RMS are paid employees of PT. Bio Farma whose product has been investigated in the study (the trivalent inactivated influenza vaccine). This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no other patents, products in development or marketing products to declare.