title: Skin Immunization Obviates Alcohol-Related Immune Dysfunction.
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.
authors.affiliation: Department of Dermatology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. rmb91@pitt.edu.|Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. rmb91@pitt.edu.|Magee Women's Research Institute, Pittsburgh, PA 15213, USA. rmb91@pitt.edu.
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Brand
authors.affiliation: Department of Dermatology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. jms176176@gmail.com.
authors.forename: John Mark
authors.initials: JM
authors.lastname: Stottlemyer
authors.affiliation: Department of Dermatology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. rachel.a.cline@gmail.com.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Cline
authors.affiliation: Department of Dermatology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. cmdst36@pitt.edu.
authors.forename: Cara
authors.initials: C
authors.lastname: Donahue
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. jab31@pitt.edu.
authors.forename: Jaideep
authors.initials: J
authors.lastname: Behari
authors.affiliation: Department of Dermatology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. lof2@pitt.edu.|Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, USA. lof2@pitt.edu.|Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. lof2@pitt.edu.|The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA. lof2@pitt.edu.|The McGowan Institute for Regenerative Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA. lof2@pitt.edu.
authors.forename: Louis D
authors.initials: LD
authors.lastname: Falo
mesh_terms: D000818:Animals; D000431:Ethanol / Q000097:blood; D005260:Female; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D008108:Liver Diseases, Alcoholic / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; D000431:Ethanol
keywords: Lieber-DeCarli; Meadows-Cook; alcohol; ethanol; intradermal immunization; skin; skin immunity; vaccination