Effective usage of cationic derivatives of polyprenols as carriers of DNA vaccines against influenza virus
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RESEARCH
Open Access
Effective usage of cationic derivatives of polyprenols as carriers of DNA vaccines against influenza virus Anna Stachyra1†, Monika Rak2†, Patrycja Redkiewicz1, Zbigniew Madeja2, Katarzyna Gawarecka1, Tadeusz Chojnacki1, Ewa Świeżewska1, Marek Masnyk3, Marek Chmielewski3, Agnieszka Sirko1 and Anna Góra-Sochacka1*
Abstract Background: 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. Methods: Several 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. Results: The 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-snglycero-3-phosphatidylcholine) induced strong humoral response to the antigen encoded by the DNA vaccine plasmid. Conclusion: The 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. Keywords: Adjuvant, Vaccine delivery, Lipofection, Immunization, Humoral response
Background 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. The main advantages of DNA vaccines are: (i) rapid and relatively inexpensive mass production and (ii) simplicity of development, modification, formulation and preparation. DNA vaccines can * Correspondence: [email protected] † Equal contributors 1 Institute of Biochemistry and Biophysics Polish Academy of Sciences, Pawińskiego 5A, 02-106 Warsaw, Poland Full list of author information is available at the end of the article
induce both humoral and cellular responses highly specific to the chosen antigen, of which the structure and posttranslational modification are like those in natural infection. The mechanism by which a DNA vaccine works has been presented in several recently published reviews, for example [1–3]. Briefly, a DNA vaccine which consists of an animal expression vector carrying a sequence encoding a selected antigen and DNA carrier is injected into the tissue, resulting in somatic
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