Intradermal administration of DNA vaccine targeting Omicron SARS-CoV-2 via pyro-drive jet injector provides the prolonged neutralizing antibody production via germinal center reaction.

Emerging SARS-CoV-2 Omicron variants are highly contagious with enhanced immune escape mechanisms against the initially approved COVID-19 vaccines. Therefore, we require stable alternative-platform vaccines that confer protection against newer variants of SARS-CoV-2. We designed an Omicron B.

Modified DNA vaccine confers improved humoral immune response and effective virus protection against SARS-CoV-2 delta variant.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic. New technologies have been utilized to develop several types of vaccines to prevent the spread of SARS-CoV-2 infection, including mRNA vaccines. Our group previously developed an effective DNA-based vaccine.

Induction of potent antitumor immunity by intradermal DNA injection using a novel needle-free pyro-drive jet injector.

The current success of mRNA vaccines against COVID-19 has highlighted the effectiveness of mRNA and DNA vaccinations. Recently, we demonstrated that a novel needle-free pyro-drive jet injector (PJI) effectively delivers plasmid DNA into the skin, resulting in protein expression higher than that achieved with a needle syringe. Here, we used ovalbumin (OVA) as a model antigen to investigate the potential of the PJI for vaccination against cancers.

pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity.

(1) Background: Cytoplasmic delivery of antigens is crucial for the induction of cellular immunity, which is an important immune response for the treatment of cancer and infectious diseases. To date, fusogenic protein-incorporated liposomes and pH-responsive polymer-modified liposomes have been used to achieve cytoplasmic delivery of antigen via membrane rupture or fusion with endosomes. However, a more versatile cytoplasmic delivery system is desired for practical use.

pH-sensitive polymer-modified liposome-based immunity-inducing system: Effects of inclusion of cationic lipid and CpG-DNA.

Efficient vaccine carriers for cancer immunotherapy require two functions: antigen delivery to dendritic cells (DCs) and the activation of DCs, a so-called adjuvant effect. We previously reported antigen delivery system using liposomes modified with pH-sensitive polymers, such as 3-methylglutarylated hyperbranched poly(glycidol) (MGlu-HPG), for the induction of antigen-specific immune responses. We reported that inclusion of cationic lipids to MGlu-HPG-modified liposomes activates DCs and enhances antitumor effects.

A two-component micelle with emergent pH responsiveness by mixing dilauroyl phosphocholine and deoxycholic acid and its delivery of proteins into the cytosol.

Providing appropriate pH responsiveness for drug delivery nanoparticles is one of the major issues in developing a new generation of delivery systems. This paper reports that, when phosphocholine and a bile acid were mixed, the resultant two-component micelle gained pH responsiveness, while the individual components did not show any such responsiveness. The pH responsiveness was shown to be determined by the chemical structure, especially the positions and chirality of the OH groups, of the bile acid, and the sensitivity was determined by the alkyl chain length of the phosphocholine.

pH-sensitive polymer-liposome-based antigen delivery systems potentiated with interferon-γ gene lipoplex for efficient cancer immunotherapy.

Potentiation of pH-sensitive liposome-based antigen carriers with IFN-γ gene lipoplexes was attempted to achieve efficient induction of tumor-specific immunity. 3-Methylglutarylated poly(glycidol) (MGluPG)-modified liposomes and cationic liposomes were used, respectively, for the delivery of antigenic protein ovalbumin (OVA) and IFN-γ-encoding plasmid DNA (pDNA). The MGluPG-modified liposomes and the cationic liposome-pDNA complexes (lipoplexes) formed hybrid complexes via electrostatic interactions after their mixing in aqueous solutions.

Potentiation of pH-sensitive polymer-modified liposomes with cationic lipid inclusion as antigen delivery carriers for cancer immunotherapy.

Cationic lipid-incorporated liposomes modified with pH-sensitive polymers were prepared by introducing 3, 5-didodecyloxybenzamidine as a cationic lipid to egg yolk phosphatidylcholine liposomes modified with 3-methylglutarylated hyperbranched poly(glycidol) (MGlu-HPG) as a pH-sensitive polymer. These liposomes were stable at neutral pH, but were destabilized below pH 6.0 because MGlu-HPG changed its characteristics from hydrophilic to hydrophobic in response to the pH decrease.

The correlation between fusion capability and transfection activity in hybrid complexes of lipoplexes and pH-sensitive liposomes.

To obtain highly potent nonviral vectors with pH-sensitive fusion ability, we prepared three hybrid complexes consisting of transferrin-conjugated pH-sensitive fusogenic polymer-modified liposomes and lipoplex using three kinds of carboxylated poly(glycidol) derivatives. These hybrid complexes were stable at neutral pH, but they became fusogenic under mildly acidic conditions. Furthermore, their fusion capability varied depending on the polymer used for their preparation.

Effect of transferrin as a ligand of pH-sensitive fusogenic liposome-lipoplex hybrid complexes.

We previously developed potent nonviral vectors based on complexation of lipoplexes and pH-sensitive fusogenic liposomes, which achieve efficient transfection through membrane fusion with intracellular acidic compartments such as endosomes. Because transferrin receptor is known to be overexpressed in cancer cells, in this study, we investigated the effect of transferrin as a ligand for transfection of various cancer-derived cell lines mediated by the liposome-lipoplex hybrid complexes. Results showed that these hybrid complexes with transferrin exhibited higher transfection efficiency toward these cells than complexes without transferrin, but the extent of the transferrin-induced enhancement was dependent on the cell line.

Gene delivery to dendritic cells mediated by complexes of lipoplexes and pH-sensitive fusogenic polymer-modified liposomes.

Dendritic cells (DCs) are potent professional antigen presenting cells that are useful for cancer immunotherapy. We previously reported the preparation and characterization of complexes of lipoplexes with pH-sensitive fusogenic liposomes, which comprise polymers based on poly(glycidol) with carboxyl groups, to transfect various malignant cell lines. The present study applied this kind of vectors to transfection of a murine DC line DC2.

Preparation of pH-sensitive poly(glycidol) derivatives with varying hydrophobicities: their ability to sensitize stable liposomes to pH.

We have previously shown that modification with succinylated poly(glycidol) (SucPG) provides stable egg yolk phosphatidylcholine (EYPC) liposomes with pH-sensitive fusogenic property. Toward production of efficient pH-sensitive liposomes, in this study, we newly prepared three carboxylated poly(glycidol) derivatives with varying hydrophobicities by reacting poly(glycidol) with glutaric anhydride, 3-methylglutaric anhydride, and 1,2-cyclohexanedicarboxylic anhydride, respectively, designated as GluPG, MGluPG, and CHexPG. Correlation between side-chain structures of these polymers and their respective abilities to sensitize stable liposomes to pH was investigated.

Generation of highly potent nonviral gene vectors by complexation of lipoplexes and transferrin-bearing fusogenic polymer-modified liposomes in aqueous glucose solution.

We reported previously that complexation of lipoplexes containing 3,5-dipentadecyloxybenzamidine (TRX-20) and transferrin-bearing succinylated poly(glycidol) (SucPG)-modified liposome, which becomes fusogenic under weakly acidic conditions, might produce gene carriers with high transfection activity. For the present study, we prepared the lipoplex-SucPG-modified liposome complexes by mixing them either in phosphate-buffered saline or in an aqueous 5% glucose solution. The complexes prepared in phosphate-buffered saline have large particles of more than 800 nm, whereas the complexes prepared in the glucose solution were remarkably small: 200-300 nm.

Enhancement of transfection activity of lipoplexes by complexation with transferrin-bearing fusogenic polymer-modified liposomes.

We previously developed complexes of lipoplexes containing 3beta-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol (DC-chol) and succinylated poly(glycidol)-modified liposome, which becomes fusogenic under weakly acidic condition, for use as a novel gene delivery system. This study explored the effect of lipoplex structures--the type of cationic lipid and cationic lipid/DNA charge ratio--on the transfection activity of those complexes. Three types of cationic lipid with different polar groups were used for the preparation of lipoplexes: DC-chol, N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP), and 3,5-dipentadecyloxybenzamidine (TRX-20) with dimethylamino group, trimethylammonium group, and benzamidine group, respectively.