Dietary Wolfberry Supplementation Enhances the Protective Effect of Flu Vaccine against Influenza Challenge in Aged Mice

Abstract

Current vaccines for influenza do not fully protect the aged against influenza infection. Although wolfberry (goji berry) has been shown to improve immune response, including enhanced antibody production, after vaccination in the aged, it is not known if this effect would translate to better protection after influenza infection, nor is its underlying mechanism well understood. To address these issues, we conducted a study using a 2 × 2 design in which aged male mice (20-22 mo) were fed a control or a 5% wolfberry diet for 30 d, then immunized with an influenza vaccine or saline (control) on days 31 and 52 of the dietary intervention, and finally challenged with influenza A/Puerto Rico/8/34 virus. Mice fed wolfberry had higher influenza antibody titers and improved symptoms (less postinfection weight loss) compared with the mice treated by vaccine alone. Furthermore, an in vitro mechanistic study showed that wolfberry supplementation enhanced maturation and activity of antigen-presenting dendritic cells (DCs) in aged mice, as indicated by phenotypic change in expression of DC activation markers major histocompatibility complex class II, cluster of differentiation (CD) 40, CD80, and CD86, and functional change in DC production of cytokines interleukin-12 and tumor necrosis factor-α as well as DC endocytosis. Also, adoptive transfer of wolfberry-treated bone marrow DCs (loaded with ovalbumin(323-339)-peptide) promoted antigen-specific T cell proliferation as well as interleukin-4 and interferon-γ production in CD4(+) T cells. In summary, our data indicate that dietary wolfberry enhances the efficacy of influenza vaccination, resulting in better host protection to prevent subsequent influenza infection; this effect may be partly attributed to improved DC function.

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“…At day 73, mice were infected with influenza A/Puerto Rico/8/34 virus and were monitored daily for weight loss and mortality. 149 Mice fed with wolfberry diet had higher influenza IgG titers, less weight loss, and improved survival rate in influenza-infected mice when compared with the mice treated by influenza vaccine alone. 149 Furthermore, an in vitro study showed that administration of 100 mg/L, 200 mg/L, 400 mg/L, or 800 mg/L wolfberry supplementation enhanced maturation and activity of antigen-presenting DCs isolated from the bone marrow of aged mice.…”

“… 149 Mice fed with wolfberry diet had higher influenza IgG titers, less weight loss, and improved survival rate in influenza-infected mice when compared with the mice treated by influenza vaccine alone. 149 Furthermore, an in vitro study showed that administration of 100 mg/L, 200 mg/L, 400 mg/L, or 800 mg/L wolfberry supplementation enhanced maturation and activity of antigen-presenting DCs isolated from the bone marrow of aged mice. Wolfberry extract dose-dependently increased the percentages of DCs expressing MHC-II and T-cell costimulatory molecules CD40, CD80, and CD86 and their expression.…”

“…However, vaccine efficacy is significantly diminished in the elderly due to the age-related impairment of both innate and adaptive immune responses. A recent study 149 has examined whether dietary wolfberry supplementation enhanced the protective effect of influenza vaccine against influenza challenge in aged male C57BL/6J mice (20–22 months old). The mice were fed a 5% milk-based preparation of wolfberry (Nestec) or fed with 5% corn starch (control) for 30 days, then immunized with an influenza vaccine or saline (control) by ip injection on days 31 and 52 of the dietary intervention, and finally challenged with influenza A/Puerto Rico/8/34 virus (Sino Biological, Bejing, People’s Republic of China) with an aluminum adjuvant at a ratio of 1:1.…”

“…Wolfberry enhanced the production of proinflammatory IL-12 and TNF-α. 149 With improved maturation of DCs, the endocytic capability of DCs was significantly reduced when treated with wolfberry extract. Adoptive transfer of wolfberry-treated bone marrow DCs loaded with ovalbumin323–339 to recipient mice promoted antigen-specific T-cell proliferation as well as IL-4 and IFN-γ production in CD4 + T cells.…”

“…Adoptive transfer of wolfberry-treated bone marrow DCs loaded with ovalbumin323–339 to recipient mice promoted antigen-specific T-cell proliferation as well as IL-4 and IFN-γ production in CD4 + T cells. 149 Wolfberry may enhance the antigen-presenting function of DCs, leading to a higher level of antigen-specific T-cell effector function involving at least Th 1 and Th 2 responses. These data indicate that dietary wolfberry potentiates the efficacy of influenza vaccination, resulting in better host protection to prevent subsequent influenza infection via improved DC function.…”