Abstract
Human milk is uniquely suited to provide optimal nutrition and immune protection to infants. Human milk oligosaccharides are structural complex and diverse consisting of short chain and long chain oligosaccharides typically present in a 9:1 ratio. 2'-Fucosyllactose (2'FL) is one of the most prominent short chain oligosaccharides and is associated with anti-infective capacity of human milk. To determine the effect of 2'FL on vaccination responsiveness (both innate and adaptive) in a murine influenza vaccination model and elucidate mechanisms involved. A dose range of 0.25-5% (w/w) dietary 2'FL was provided to 6-week-old female C57Bl/6JOlaHsd mice 2 weeks prior primary and booster vaccination until the end of the experiment. Intradermal (i.d.) challenge was performed to measure the vaccine-specific delayed-type hypersensitivity (DTH). Antigen-specific antibody levels in serum as well as immune cell populations within several organs were evaluated using ELISA and flow cytometry, respectively. In an ex vivo restimulation assay, spleen cells were cocultured with influenza-loaded bone marrow-derived dendritic cells (BMDCs) to study the effects of 2'FL on vaccine-specific CD4+ and CD8+ T-cell proliferation and cytokine secretions. Furthermore, the direct immune regulatory effects of 2'FL were confirmed using in vitro BMDCs T-cell cocultures. Dietary 2'FL significantly (p < 0.05) enhanced vaccine specific DTH responses accompanied by increased serum levels of vaccine-specific immunoglobulin (Ig) G1 and IgG2a in a dose-dependent manner. Consistently, increased activation marker (CD27) expression on splenic B-cells was detected in mice receiving 2'FL as compared to control mice. Moreover, proliferation of vaccine-specific CD4+ and CD8+ T-cells, as well as interferon-γ production after ex vivo restimulation were significantly increased in spleen cells of mice receiving 2'FL as compared to control mice, which were in line with changes detected within dendritic cell populations. Finally, we confirmed a direct effect of 2'FL on the maturation status and antigen presenting capacity of BMDCs. Dietary intervention with 2'FL improves both humoral and cellular immune responses to vaccination in mice, which might be attributed in part to the direct effects of 2'FL on immune cell differentiation.
Highlights
Vulnerable populations with an immature or incompetent immune system renders them at increased risk for infections while limited responsiveness to vaccines is often detected [1]
Quadratic regression was performed and identified a linear increase in Delayed-type hypersensitivity (DTH) up to 1% providing a pharmaceutical optimum at 2.5% 2′FL
Subclass specific IgG2a and IgG1-antibody concentrations were detected in serum of vaccinated mice receiving control diet and compared to sham-vaccinated mice indicating that induced antibodies are vaccine-specific
Summary
Vulnerable populations with an immature or incompetent immune system (such as infants, preterm born infants, immune compromised individuals, and elderly) renders them at increased risk for infections while limited responsiveness to vaccines is often detected [1]. The neonatal immunological milieu is polarized toward a Th2-type immunity with dampening of Th1-type immune responses [e.g., interferon-γ (IFN-γ) production] and cytotoxicity (CD8+ T-cell) [2, 3], resulting in qualitatively and quantitatively limited cellular responses to infections compared to older infants. Strategies aimed at inducing protective humoral and optimal cellular immune responses may facilitate the improvement of neonatal vaccine efficacy. Dietary interventions that can improve the immune system and shape an optimal gut microbiota is a promising strategy to improve vaccine efficacy. Human milk is uniquely suited to provide optimal nutrition and immune protection to infants. 2′-Fucosyllactose (2′FL) is one of the most prominent short chain oligosaccharides and is associated with anti-infective capacity of human milk. Human milk oligosaccharides are structural complex and diverse consisting of short chain and long chain oligosaccharides typically present in a 9:1 ratio. 2′-Fucosyllactose (2′FL) is one of the most prominent short chain oligosaccharides and is associated with anti-infective capacity of human milk.
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