Abstract
Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH)-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD) and liver-sparing Meadows-Cook (MC) diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA) by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM), directly to liver (hydrodynamic), or cutaneously (biolistic, ID). We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg), and myeloid-derived suppressor cell (MDSC) populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH), antigen-specific cytotoxic T lymphocyte (CTL), and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects.
Highlights
IntroductionChronic alcohol abuse increases viral [1,2,3,4,5] and bacterial [6,7,8] infection rates, impairs host immune responses, and can augment co-incident disease progression leading to greater morbidity and mortality
Our results suggest that independent of alcohol feeding method, skin immunization obviates alcohol-induced immune suppression observed with systemic immunization, suggesting a novel strategy to improve vaccine effectiveness in alcoholic patients
We previously demonstrated that EtOH administration to rats through either acute [35] and/or chronic (LD) feeding regimes [22] leads to significantly greater EtOH levels in blood than in skin
Summary
Chronic alcohol abuse increases viral [1,2,3,4,5] and bacterial [6,7,8] infection rates, impairs host immune responses, and can augment co-incident disease progression leading to greater morbidity and mortality. In attempts to improve the efficacy of traditional intramuscular (IM) vaccinations in alcoholics, high dose and accelerated IM vaccination schedules have been attempted and show some success in improving seroconversion rates in alcohol-consuming non-responders [13,14]. Skin-targeted immunization could result in more efficacious vaccines in alcoholic patients by taking advantage of low skin alcohol levels [22] and an extensive skin DC network
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