Lipopolysaccharide contamination in intradermal DNA vaccination: toxic impurity or adjuvant?
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
van den Berg
Joost H
JH
Department of Pharmacy & Pharmacology, Slotervaart Hospital/the Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. joost.vandenberg@slz.nl
Quaak
Susanne G L
SG
Beijnen
Jos H
JH
Hennink
Wim E
WE
Storm
Gert
G
Schumacher
Ton N
TN
Haanen
John B A G
JB
Nuijen
Bastiaan
B
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007271:Injections, Intradermal; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D019444:Vaccines, DNA; D014758:Viral Core Proteins; C102366:nucleoprotein (366-374), influenza virus