title: A novel adjuvant, the general opioid antagonist naloxone, elicits a robust cellular immune response for a DNA vaccine.
abstract: While many adjuvants have been discovered and used in research, only a few adjuvants have been permitted for use with human vaccination. We have previously shown that the administration of naloxone (NLX), a general opioid antagonist, during infection with a non-virulent strain of herpes simplex virus type 1 (HSV-1) could enhance protection against HSV-1 challenge. Here, the adjuvant activity of NLX has been evaluated using a DNA vaccine for HSV-1 as a model. BALB/c mice were divided into four groups; for experimental groups, mice received the glycoprotein D1 (gD1) DNA vaccine alone or in combination with the adjuvant NLX. A positive control group received the KOS strain of HSV-1, and a negative control group received PBS. All mice were immunized three times on days 0, 21 and 42. Three weeks after the last immunization, immune responses against HSV-1 were assessed. Our results indicate that the administration of NLX as an adjuvant increased the ability of the gD1 DNA vaccine to enhance cytolytic T lymphocyte activity, lymphocyte proliferation, delayed-type hypersensitivity and shifting the immune response toward a T helper (Th)1 pattern and improved protective immunity against HSV-1. NLX also increased the IgG2a/IgG1 ratio, though it did not affect the production of HSV-1 antiserum. In conclusion, administration of NLX as an adjuvant in combination with the gD1 DNA vaccine can enhance cell-mediated immunity and shift the immune responses to Th1.
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Jamali
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mahdavi
authors.forename: Zuhair Muhammad
authors.initials: ZM
authors.lastname: Hassan
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Sabahi
authors.forename: Mohammad Jazayeri
authors.initials: MJ
authors.lastname: Farsani
authors.forename: Taravat
authors.initials: T
authors.lastname: Bamdad
authors.forename: Hoorieh
authors.initials: H
authors.lastname: Soleimanjahi
authors.forename: Morteza
authors.initials: M
authors.lastname: Motazakker
authors.forename: Shahram
authors.initials: S
authors.lastname: Shahabi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology / Q000517:prevention & control; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D007111:Immunity, Cellular / Q000187:drug effects; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009270:Naloxone / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage*; D014759:Viral Envelope Proteins / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D009292:Narcotic Antagonists; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C044768:glycoprotein E, herpes simplex virus type 1; D009270:Naloxone