Leptin-based adjuvants: An innovative approach to improve vaccine response

Abstract

Leptin is a pleiotropic hormone with multiple direct and regulatory immune functions. Leptin deficiency or resistance hinders the immunologic, metabolic, and neuroendocrinologic processes necessary to thwart infections and their associated complications, and to possibly protect against infectious diseases following vaccination. Circulating leptin levels are proportional to body fat mass. High circulating leptin concentrations, as observed in obesity, are indicative of the development of leptin transport saturation/signaling desensitization. Leptin bridges nutritional status and immunity. Although its role in vaccine response is currently unknown, over-nutrition has been shown to suppress vaccine-induced immune responses. For instance, obesity (BMI ≥ 30 kg/m2) is associated with lower antigen-specific antibody titers following influenza, hepatitis B, and tetanus vaccinations. This suggests that obesity, and possibly saturable leptin levels, are contributing factors to poor vaccine immunogenicity. While leptin-based therapies have not been investigated as vaccine adjuvants thus far, leptin’s role in immunity suggests that application of these therapies is promising and worth investigation to enhance vaccine response in people with leptin signaling impairments. This review will examine the possibility of using leptin as a vaccine adjuvant by: briefly reviewing the distribution and signal transduction of leptin and its receptors; discussing the physiology of leptin with emphasis on its immune functions; reviewing the causes of attenuation of leptin signaling; and finally, providing plausible inferences for the innovative use of leptin-based pharmacotherapies as vaccine adjuvants.

The weight of obesity on the human immune response to vaccination

“…The pro-inflammatory hormone leptin, which has many immunologic functions, has been shown to correlate with body fat mass since it is produced and secreted from adipocytes [3]. Obesity may interfere with an obese individual’s ability to mount an effective immune response to vaccination or an infection due to increased body fat and the increased production of leptin [4]. Further, there is some evidence for the involvement of leptin and leptin-related gene polymorphisms in the serum leptin concentrations [3].…”

Vitamin D, leptin and impact on immune response to seasonal influenza A/H1N1 vaccine in older persons

“…16 Leptin, a hormone produced in adipose tissue, has notable immunomodulatory effects. 17 We have previously demonstrated our findings on the association of leptin and leptin-related gene polymorphisms on the immune response to influenza A/H1N1 vaccine in older persons. 18 In this study, we examined the effect of baseline serum 25-(OH) D status on both humoral and CMI responses following a single vaccination with the licensed seasonal trivalent 2010-2011 influenza vaccine (containing influenza A/California/ H1N1 like virus) in a healthy older cohort.…”

“…Leptin is produced by adipocytes and, along with its well established roles in metabolism, it has also been shown to have immunomodulatory effects. 17 Leptin levels are known to be higher with increasing adiposity. Elevated leptin levels in the obese state have been observed to result in attenuated leptin signaling (leptin resistance) and impairment in both innate and adaptive influenza-specific immunity.…”

“…34 Leptin receptors and VDR are widely distributed in various tissues. There is supportive evidence that leptin and vitamin D signaling and metabolism pathways interact and influence each other; in one study leptin reduced gene expression of 1-alpha-hydroxylase and production of 1,25-(OH) 2 D. 35 However, hyperleptinemia in the context of leptin resistance 17,36 may modify the relationship between serum 25-(OH) D and leptin. We found suggestion of a positive correlation between baseline 25-(OH) D levels and baseline leptin levels (r D 0.15, p D 0.08).…”

Protein Energy Malnutrition during Vaccination Has Limited Influence on Vaccine Efficacy but Abolishes Immunity if Administered during Mycobacterium tuberculosis Infection

“…Leptin is a hormone whose primary role is to regulate glucose uptake and fat deposition, and reduced levels thereof have been reported in malnourished individuals (22). Recent data suggest that leptin, in addition to its metabolic functions, is essential for activation of effector T cells (21), and leptin has even been suggested as a potential vaccine adjuvant (49). It would be highly relevant in future TB PEM studies to monitor leptin levels and the potential role of leptin supplementation.…”