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.

Cloning, Expression and Purification of a Novel Multi-epitopic HIV-1 Vaccine Candidate: A Preliminary Study on Immunoreactivity

“…The IFN-γ cytokine is an indicative of Th1 cellular immune responses and the induction of TCD8 + cells that have a key role in control and elimination of viral infections [18]. Many studies have shown the importance of IFN-γ in the control of viral infection [19]. Ullum et al [20] have measured the amount of IFN-γ in healthy, HIV-infected and AIDS patients and have shown that a decrease in IFN-γ was significantly correlated with progression to AIDS.…”

Immune Responses of Mice Immunized with HBsAg Formulated in Naloxone/Alum Mixture: Comparison to Fendrix Vaccine

“…For instance, vaccination against intracellular infection requires strong Th1 responses, and Freund's adjuvant can provide it, but the major obstacle is that it is not approved for human use. One of the best food and drug administration (FDA) approved vaccine adjuvants is aluminum salt (Alum), which mostly enhances Th2-specific responses (16). Currently, the standard HBV vaccine contains 20 microgram of hepatitis B surface antigen (HBsAg) in combination with 0.5 milligram of aluminum salt as an adjuvant (17).…”

“…However, the mechanism of immunostimulating effect of naloxone is poorly understood. Fortunately, naloxone is a well-tolerated drug considering toxicity and adverse effects, and it is also FDA approved (16,20,22,23). During the last decade, many studies have used this agent as adjuvant in the formulation of different vaccines.…”

“…During the last decade, many studies have used this agent as adjuvant in the formulation of different vaccines. They showed that naloxone can induce TH1 pattern of immunity and increase the IFN-γ level (14,16,22,(24)(25)(26).…”

HPV16E7d Candidate Vaccine Modified Genes Expression in Tumor Environment: Flic as Adjuvant Changed TGF-B Gene Expression

“…Adjuvants used in combination or mixture with vaccines by various mechanisms improve immune responses. 10,11 Such adjuvants are microbial product which bind to the Toll like receptors and induce inflammation. The microbial products that bind to the TLR5 is flagellin (FliC).…”