Maternal Supplementation with LGG Reduces Vaccine-Specific Immune Responses in Infants at High-Risk of Developing Allergic Disease

Abstract

Probiotics are defined as live micro-organisms that when administered in adequate amounts confer a health benefit on the host. Among their pleiotropic effects, inhibition of pathogen colonization at the mucosal surface as well as modulation of immune responses are widely recognized as the principal biological activities of probiotic bacteria. In recent times, the immune effects of probiotics have led to their application as vaccine adjuvants, offering a novel strategy for enhancing the efficacy of current vaccines. Such an approach is particularly relevant in regions where infectious disease burden is greatest and where access to complete vaccination programs is limited. In this study, we report the effects of the probiotic, Lactobacillus rhamnosus GG (LGG) on immune responses to tetanus, Haemophilus influenzae type b (Hib) and pneumococcal conjugate (PCV7) vaccines in infants. This study was conducted as part of a larger clinical trial assessing the impact of maternal LGG supplementation in preventing the development of atopic eczema in infants at high-risk for developing allergic disease. Maternal LGG supplementation was associated with reduced antibody responses against tetanus, Hib, and pneumococcal serotypes contained in PCV7 (N = 31) compared to placebo treatment (N = 30) but not total IgG levels. Maternal LGG supplementation was also associated with a trend to increased number of tetanus toxoid-specific T regulatory in the peripheral blood compared to placebo-treated infants. These findings suggest that maternal LGG supplementation may not be beneficial in terms of improving vaccine-specific immunity in infants. Further clinical studies are needed to confirm these findings. As probiotic immune effects can be species/strain specific, our findings do not exclude the potential use of other probiotic bacteria to modulate infant immune responses to vaccines.

Influence of the microbiota on vaccine effectiveness

“…However, the mechanisms behind the proposed beneficial effects of probiotics in vaccination remain unknown. Although some of these studies report significant increases in vaccine-specific antibodies [57][58][59][60], the majority show modest or no effect of probiotics in providing major enhancement of antibody responses to vaccines [61][62][63][64][65]. Moreover, the outcomes of these studies are highly dependent on experimental conditions including strain and dose of probiotics, type of vaccine, and population studied.…”

“…Total IgG was similar in both groups [65] LGG (ATCC 52103) 5 Â 10 9 cfu, LGG (LC705) 5 Â 10 9 cfu, Bifidobacterium breve (Bbi99) 2 Â 10 8 cfu and Propionibacterium freudenreichii ssp. Shermanii JS 2 Â 10 9 cfu (n = 47).…”

Adjuvant Probiotics and the Intestinal Microbiome: Enhancing Vaccines and Immunotherapy Outcomes

“…From a study within a larger clinical trial, the Lactobacillus rhamnosus GG (LGG) effect on immune responses to tetanus, Haemophilus influenza type b and pneumococcal conjugate vaccines in infants was assessed, in conjunction with the impact of maternal LGG supplementation in preventing the development of atopic eczema in infants at high-risk for developing allergic disease [ 52 ]. The study reported that maternal LGG supplementation was associated with reduced antibody responses against tetanus, Haemophilus influenza b, and pneumococcal conjugate compared to placebo treatment but not total IgG levels.…”

Vaccine Interactions With the Infant Microbiome: Do They Define Health and Disease?

“…In contrast, a few studies have even reported a negative association between probiotics and vaccine responses. Maternal supplementation with Lactobacillus rhamnosus GG (LGG) was associated with a reduction in infant antibody responses to tetanus, Hib, and pneumococcus vaccines (88), and Bangladeshi children who received a 4-week course of BBG-01 had reduced levels of cholera toxin subunit B-specific IgA levels compared to controls (89). The administration of probiotics was associated with an increase in secretory IgA in stool samples of children at 5 months of age (90); however, this did not translate to improved clinical outcomes, as infants exposed to probiotics reported a higher frequency of mucosal infections up to 2 years of age, despite both groups being able to clear infections at comparable rates (90).…”