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: Abbas Jamali, Mehdi Mahdavi, Zuhair Muhammad Hassan, Farzaneh Sabahi, Mohammad Jazayeri Farsani, Taravat Bamdad, Hoorieh Soleimanjahi, Morteza Motazakker, Shahram Shahabi
• Journal: International immunology (Int Immunol) Vol. 21 Issue 3 Pg. 217-25 (Mar 2009) ISSN: 1460-2377 [Electronic] England
• PMID: 19174474 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Immunoglobulin G
• Narcotic Antagonists
• Vaccines, DNA
• Viral Envelope Proteins
• glycoprotein E, herpes simplex virus type 1
• Naloxone

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Cell Proliferation (drug effects)
• Cytotoxicity, Immunologic (drug effects, immunology)
• Herpes Simplex (immunology, prevention & control)
• Herpesvirus 1, Human (immunology)
• Hypersensitivity, Delayed (prevention & control)
• Immunity, Cellular (drug effects)
• Immunization, Secondary
• Immunoglobulin G (blood)
• Mice
• Mice, Inbred BALB C
• Naloxone (administration & dosage)
• Narcotic Antagonists (administration & dosage)
• T-Lymphocytes, Cytotoxic (cytology, immunology, metabolism)
• Th1 Cells (immunology)
• Vaccines, DNA (administration & dosage)
• Viral Envelope Proteins (administration & dosage)