PURPOSE: Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal DNA vaccination administered by DNA tattooing. METHOD: Mice were vaccinated with a model DNA vaccine (Luc-NP) with an increasing content of residual LPS. The effect of LPS on systemic toxicity, antigen expression and cellular immunity was studied. RESULTS: The presence of LPS in the DNA vaccine neither induced systemic toxicity (as reflected by IL-6 concentration in serum), nor influenced antigen expression (measured by intravital imaging). Higher LPS contents however, appeared to be associated with an elevated cytotoxic T-lymphocyte (CTL) response but without reaching statistical significance. Interestingly, the DNA tattoo procedure by itself was shown to induce a serum cytokine response that was at least as potent as that induced by parenteral LPS administration. CONCLUSION: LPS does not show toxicity in mice vaccinated by DNA tattooing at dose levels well above those encountered in GMP-grade DNA preparations. Thus, residual LPS levels in the pharmaceutical range are not expected to adversely affect clinical outcome of vaccination trials and may in fact have some beneficial adjuvant effect. The observed pro-inflammatory effects of DNA tattoo may help explain the high immunogenicity of this procedure. Copyright 2009 Elsevier B.V. All rights reserved.
PURPOSE:Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal DNA vaccination administered by DNA tattooing. METHOD:Mice were vaccinated with a model DNA vaccine (Luc-NP) with an increasing content of residual LPS. The effect of LPS on systemic toxicity, antigen expression and cellular immunity was studied. RESULTS: The presence of LPS in the DNA vaccine neither induced systemic toxicity (as reflected by IL-6 concentration in serum), nor influenced antigen expression (measured by intravital imaging). Higher LPS contents however, appeared to be associated with an elevated cytotoxic T-lymphocyte (CTL) response but without reaching statistical significance. Interestingly, the DNA tattoo procedure by itself was shown to induce a serum cytokine response that was at least as potent as that induced by parenteral LPS administration. CONCLUSION:LPS does not show toxicity in mice vaccinated by DNA tattooing at dose levels well above those encountered in GMP-grade DNA preparations. Thus, residual LPS levels in the pharmaceutical range are not expected to adversely affect clinical outcome of vaccination trials and may in fact have some beneficial adjuvant effect. The observed pro-inflammatory effects of DNA tattoo may help explain the high immunogenicity of this procedure. Copyright 2009 Elsevier B.V. All rights reserved.
Authors: Stephanie van de Wall; Mateusz Walczak; Nienke van Rooij; Baukje-Nynke Hoogeboom; Tjarko Meijerhof; Hans W Nijman; Toos Daemen Journal: Vaccines (Basel) Date: 2015-03-24