Abstract
BackgroundCationic derivatives of polyprenols (trimethylpolyprenylammonium iodides – PTAI) with variable chain length between 6 and 15 isoprene units prepared from naturally occurring poly-cis-prenols were tested as DNA vaccine carriers in chickens and mice. This study aimed to investigate if PTAI could be used as an efficient carrier of a DNA vaccine.MethodsSeveral vaccine mixtures were prepared by combining different proportions of the vaccine plasmid (carrying cDNA encoding a vaccine antigen, hemagglutinin from H5N1 influenza virus) and various compositions of PTAI. The vaccines were delivered by intramuscular injection to either chickens or mice. The presence of specific antibodies in sera collected from the immunized animals was analyzed by enzyme-linked immunosorbent assay (ELISA) and hemagglutination inhibition (HI) test.ResultsThe mixtures of PTAI with helper lipids, such as DOPE (1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine), DC-cholesterol [{3ß-[N-(N′,N′-dimethylaminoethane)-carbamoyl] cholesterol} hydrochloride] or DOPC (1,2-dioleoyl-sn-glycero-3-phosphatidylcholine) induced strong humoral response to the antigen encoded by the DNA vaccine plasmid.ConclusionThe animal immunization results confirmed that PTAI compositions, especially mixtures of PTAI with DOPE and DC-cholesterol, do work as effective carriers of DNA vaccines, comparable to the commercially available lipid transfection reagent.
Highlights
Cationic derivatives of polyprenols with variable chain length between 6 and 15 isoprene units prepared from naturally occurring poly-cis-prenols were tested as DNA vaccine carriers in chickens and mice
In this work we investigated if Cationic derivatives of polyprenols (PTAI) with diverse length polyprenyl chains (6–15 units) can be used as effective carriers of DNA vaccines
In the first experiment four different PTAI compositions: (i) PTAI-6-8/DOPE, (ii) PTAI-11/DOPE/DC, (iii) PTAI-11/ DOPE/DC/DOPC and (iv) PTAI-15/DOPE/DC/DOPC mixed with 125 μg of K3 were tested along with the positive (K3 mixed with Lipofectin® Transfection Reagent) and negative controls
Summary
Cationic derivatives of polyprenols (trimethylpolyprenylammonium iodides – PTAI) with variable chain length between 6 and 15 isoprene units prepared from naturally occurring poly-cis-prenols were tested as DNA vaccine carriers in chickens and mice. This study aimed to investigate if PTAI could be used as an efficient carrier of a DNA vaccine. In the past two decades considerable development of DNA vaccine technology has been observed. This technology has emerged as a promising alternative to traditional vaccines and can be applied for therapy of human and animal infections, cancers, allergies or autoimmune disorders. In comparison to live attenuated or inactivated vaccines the immunogenicity of DNA vaccines, especially in humans and large animals, is usually lower. Improvement of both the expression level of an antigen and the efficiency of transfection are essential for elevation of DNA immunization efficacy. Various modifications of expression cassettes (e.g. codon optimization, introducing of various regulatory elements, other changes in the antigen coding sequence), biological and biochemical adjuvants, different carriers and vaccination routes and other strategies were widely investigated [4]
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