A novel adjuvant, the general opioid antagonist naloxone, elicits a robust cellular immune response for a DNA vaccine

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, delayedtype
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.