L actobacillus in Jelly Enhances the Effect of Influenza Vaccination in Elderly Individuals

To the Editor: Decline in immune function in elderly individuals increases their susceptibility to infectious diseases, so it is important to take protective measures against susceptibility to infectious disease, including viral infection. Influenza virus (IFV) infection often causes pneumonia in elderly individuals during the winter months, which accounts for a large proportion of deaths in this population group. Vaccination is one of the best ways of eliminating this cause, but antibody titers in elderly individuals do not always increase sufficiently after immunization.1 Probiotics are live bacteria that, when administered in adequate amounts, are beneficial to the host.2 Several studies have reported that probiotics such as bifidobacteria and lactobacilli could elicit immune responses, such as the action of phagocytes and natural killer (NK) cells,3 and enhance the effects of influenza vaccination.4 Lactobacillus paracasei MoLac-1 was selected as a strain showing immunostimulatory effects, and oral administration of heat-killed MoLac-1 ameliorated the symptoms of IFV infection in mice.5 The effect of heat-killed MoLac-1 on immune function in elderly individuals was investigated in the current study. A commercial jelly containing 10 billion heat-killed MoLac-1 cells and a placebo jelly without MoLac-1 cells were used. Fifteen elderly nursing home resident volunteers were enrolled in the study. Participants were stratified according to age, sex, body mass index (BMI), and blood albumin and were randomly assigned to receive the test jelly (MoLac group; n = 8) or the placebo jelly (placebo group; n = 7) for 12 weeks (November 2012 to February 2013). Baseline characteristics were comparable with regard to mean age (75.6 ± 6.7 in the MoLac group vs 75.9 ± 7.7 in placebo group), sex (50.0% vs 42.9% female), mean BMI (24.3 ± 2.9 kg/m2 vs 24.3 ± 2.9 kg/m2), and mean blood albumin (4.14 ± 0.23 g/dL vs 4.07 ± 0.37 g/dL). Three weeks after starting jelly intake (Week 3), all participants were administered the IFV vaccine, which included three viral antigens (A/H1N1, A/H3N2, and B). Blood samples were collected at Weeks 0, 6, and 12 and analyzed immunologically. The ethical committee of Fukushimura Hospital approved the study protocol, and written informed consent was obtained from all subjects or their relatives (approval number 305 at October 25, 2012). This study was registered at the UMIN Clinical Trial Registry (UMIN000009252). Paired t-tests were used for comparison with baseline values, and Student t-tests were used for between-group comparisons. P < .05 was considered statistically significant. Although some changes were observed during the trial period, significant between-group differences were not observed in changes from baseline values in NK cell activity levels, neutrophil bactericidal activity levels, and neutrophil phagocytosis activity levels (data not shown). Immunoglobulin G, M, and A levels did not change significantly in either group during the study period (data not shown). Three weeks after the vaccination (Week 6), hemagglutination inhibition (HI) titers against all three types of influenza antigens (A/H1N1, A/H3N2, and B) were significantly higher in the MoLac group than at baseline, whereas only the HI titers against A/H3N2 were higher in the placebo group. Although not significant, the changes from baseline values in the antibody titers against A/H3N2 tended to be higher (P = .09) in the MoLac group than in the placebo group (Figure 1). The rate of seroconversion 6 against influenza antigens (A/H1N1, A/H3N2, and B) at Week 6 was not statistically significant (50.0% vs 28.6%, 87.5% vs 42.9%, and 37.5% vs 14.3% in the MoLac and placebo groups, respectively). Some probiotics have been reported to elicit innate and acquired immune responses. In the present study, the intake of heat-killed lactobacilli did not affect the function of innate immunity in elderly individuals but had a tendency to enhance immune responses induced by vaccination. The dead cells in the probiotics might modulate acquired immunity of the host but not innate immunity. To the best of the knowledge of the authors, no clinical studies have been done to investigate the effects of probiotics dead cells on the immune responses induced by antigens. Because the scale of this study was limited, significant effects were not observed, although the results show the possibility that probiotic dead cells are an effective means of improving the function of acquired immunity in elderly individuals. Nonviable microorganisms could be used more easily than viable ones in food or food supplements. Further larger-scale clinical studies are needed to confirm the present findings. We thank the patients and their guardians and the medical staff and attending physicians for their cooperation. We are grateful to Ms. Otani, Ms. Shoko Sonoda, Ms. Takahashi, Mr. Norihiro Ogawa, and Mr. Takeshi Kanesaka for their excellent technical assistance. The results have been submitted for presentation at the 35th meeting of The European Society for Clinical Nutrition and Metabolism, Leipzig, Germany, August 31 to September 3, 2013. Conflicts of Interest: This work was partially supported by Research Funding for Longevity Sciences (24–8) of the National Center for Geriatrics and Gerontology, Japan, and by funding from Clinico Co., Ltd., Tokyo, Japan. The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper.