title: Naloxone and alum synergistically augment adjuvant activities of each other in a mouse vaccine model of Salmonella typhimurium infection.
abstract: Alum is the most commonly used adjuvant for human vaccination but is a poor inducer of cell mediated immunity and T helper 1 (Th1) responses. We have previously shown that naloxone (NLX), which is a general opioid antagonist, acts as an effective adjuvant in enhancing vaccine-induced cellular immunity and Th1 immune responses. Here, we tested the efficacy of an alum-NLX mixture, as a new adjuvant, in the induction of humoral and cellular immunity in response to endotoxin-removed lysate (ERL) of Salmonella typhimurium (S. typhimurium) as a model vaccine. BALB/c mice were divided into five vaccination groups. Mice in the experimental groups received either the ERL vaccine alone or in combination with the adjuvant alum, NLX or the alum-NLX mixture. Mice in the negative control group received phosphate-buffered saline. All mice were immunized on days 0 and 7. Two weeks after the last immunization, immune responses to S. typhimurium were assessed. Our results indicate that including the alum-NLX mixture as an adjuvant during vaccination increased the ability of the ERL vaccine to enhance lymphocyte proliferation, shifted the immune response toward a Th1 profile and increased S. typhimurium-specific IgG, IgG2a and the ratio of IgG2a to IgG1. This resulted in improved protective immunity against S. typhimurium. In conclusion, administering an alum-NLX mixture adjuvant in combination with the ERL vaccine enhances both humoral and cellular immunity, and shifts the immune response to a Th1 pattern.
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
authors.forename: Nima Hosseini
authors.initials: NH
authors.lastname: Jazani
authors.forename: Somayeh
authors.initials: S
authors.lastname: Parsania
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sohrabpour
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Mazloomi
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Karimzad
authors.forename: Shahram
authors.initials: S
authors.lastname: Shahabi
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism* / Q000494:pharmacology; D000534:Alum Compounds / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004731:Endotoxins / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D007928:Lethal Dose 50; D008099:Liver / Q000382:microbiology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009270:Naloxone / Q000378:metabolism* / Q000494:pharmacology; D012480:Salmonella Infections / Q000276:immunology*; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*; D013154:Spleen / Q000382:microbiology
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000907:Antibodies, Bacterial; D016207:Cytokines; D004731:Endotoxins; D007074:Immunoglobulin G; D022562:Salmonella Vaccines; D009270:Naloxone