Marked Enhancement of the Antigen-Specific Immune Response by Combining Plasmid DNA-Based Immunization with a Schiff Base-Forming Drug

Abstract

Although plasmid DNA (pDNA)-based immunization has proven efficacy, the level of immune responses that is achieved by this route of vaccination is often lower than that induced by traditional vaccines, especially for primates and humans. We report here a simple and potent method to enhance pDNA-based vaccination by using two different plasmids encoding viral or bacterial antigens. This method is based on coadministration of low concentrations of a recently described immunopotentiating, Schiff base-forming drug called tucaresol which has led to significant augmentation of antigen-specific humoral and cellular immune responses. Our data suggest that enhancement of the immune response with tucaresol might provide a powerful tool for the further development of pDNA-based immunization for humans.

Protective Efficacy of a DNA Influenza Virus Vaccine Is Markedly Increased by the Coadministration of a Schiff Base-Forming Drug

“…It has recently been shown that tucaresol efficiently enhances the immune response to pDNA immunization (6). This was manifested as an increased humoral and cellular response to the mycobacterial heat shock protein 65 (Mhsp65) and Epstein-Barr virus nuclear antigen 4 (EBNA-4) genes determined using in vitro assays for antibody production, cytokine release, T-cell proliferation, and cytotoxicity.…”

“…Other approaches to enhance DNA vaccination include the use of cytokine-encoding plasmids such as granulocyte-macrophage colony-stimulating factor, which has been shown to enhance the protective efficacy of an influenza DNA vaccine (21). Tucaresol was previously compared to gamma interferon and granulocyte-macrophage colony-stimulating factor for their efficiency as DNA vaccine adjuvants, and tucaresol was found to be at least as strong an adjuvant as either of these two cytokines (6). It has been shown that NP-based DNA immunization results in heterologous protection that is T-cell mediated (15,32).…”

“…Tucaresol (Tuc) is a Schiff base-forming molecule that is capable of interacting with molecules expressed on the surface of T cells in a process that leads to costimulation (24,25). We have recently identified tucaresol as a potent enhancer for humoral and cellular immune responses induced by pDNA immunization (6). Tucaresol markedly enhanced the antigen specific immune response as measured in vitro by its ability to elevate the immune response against viral and bacterial antigens (6).…”

“…We have recently identified tucaresol as a potent enhancer for humoral and cellular immune responses induced by pDNA immunization (6). Tucaresol markedly enhanced the antigen specific immune response as measured in vitro by its ability to elevate the immune response against viral and bacterial antigens (6).…”

“…Yet, pDNA immunization suffers from a limited efficacy due to the induction of a weaker immune response than that induced by some traditional vaccines such as live-virus vaccines (6,10). This has contributed to the premise that pDNA immunization is probably not an appropriate vaccination strategy against influenza virus infection (22).…”