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. © The Japanese Society for Immunology. 2009. All rights reserved.