Effective usage of cationic derivatives of polyprenols as carriers of DNA vaccines against influenza virus

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.

Polyprenol-Based Lipofecting Agents for In Vivo Delivery of Therapeutic DNA to Treat Hypertensive Rats

“…The compositions were stored at 4 °C up to 7 days. These compositions were previously shown to be effective DNA vaccine carriers (Stachyra et al 2017 ). They (and their use) are the subject of patents (No.…”

“…They are involved in cell response to environmental stress, glycosylation, and prenylation of proteins, and also they intensify the fusion and increase the permeability of model membranes (Swiezewska and Danikiewicz 2005 ). Recent studies (Gawrys et al 2014b , 2018 ; Grecka et al 2016 ; Rak et al 2016 ; Stachyra et al 2017 ) show that cationic derivatives of polyisoprenoid alcohols, called PTAI, are non-toxic and may serve as lipofectants. In the present study, the effectiveness of two PTAI mixtures was investigated for plasmid DNA delivery into rats’ cells and to rats and compared to the commercially available reagents for transfection: in vivo-jetPEI® (Polyplus-transfection) and Avalanche®-in vivo Transfection Reagent (EZ Biosystems LLC).…”

Response to a DNA vaccine against the H5N1 virus depending on the chicken line and number of doses

“…Many DNA vaccine candidates for protecting chickens from avian influenza have been described [10,13,14], and one such vaccine has been licensed for use in the U.S. [15]. Protective DNA vaccine candidates were also designed and tested by our team [16][17][18][19][20].…”

Construction of an Effective Delivery System for DNA Vaccines Using Biodegradable Polylactic Acid Based Microspheres

“…(1) the potential to induce a broad immune response without the risks observed using replicating microorganisms [1] ; (2) the ability to simultaneously stimulate humoral and cellular immunity [2] ; (3) the process of purifying plasmid DNA is simple, inexpensive, and suitable for mass production [3] ; (4) DNA molecules are stable, therefore easy to transport and preserve [4] ; and (5) by simply mixing multiple plasmid DNA samples, antigens with similar biochemical properties can be combined to form a multivalent vaccine [5] . Based on these advantages, DNA vaccines may be substitutes for traditional vaccines and may have a wide range of applications in the treatment of infectious diseases in humans and animals [6] . For example, Zhang et al have developed a DNA vaccine for Clostridium di cile, which encodes two C. di cile toxin receptor binding domains and showed good results in mouse and hamster model experiments [7] .…”