Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses

Abstract

BackgroundImmunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI) is a cationic polymer which effectively delivers the plasmid DNA.ResultsIn the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The size of the PEI/pci-S nanoparticles appeared to be around 194.7 ± 99.3 nm, and the expression of the S mRNA and protein was confirmed in vitro. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (P < 0.05) higher S-specific IgG1 in the sera and mucosal secretory IgA in the lung wash than those in mice treated with pci-S alone. Compared to those in mice challenged with pci-S alone, the number of B220+ cells found in PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86) and class II major histocompatibility complex molecules (I-Ad) were increased on CD11c+ dendritic cells in cervical lymph node from the mice after PEI/pci-S vaccination. The percentage of IFN-γ-, TNF-α- and IL-2-producing cells were higher in PEI/pci-S vaccinated mice than in control mice.ConclusionThese results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses.

Polyethylenimine-based micro/nanoparticles as vaccine adjuvants

“…For example, in respiratory infection, intranasal administration was prone to elicit mucosal secretory antibodies, as well as more serum antibodies. 54 A similar trend was found for the HIV vaccines which elicited more antibodies in the vagina. 74 The detected markers prove the efficacy of these vaccines usually through two main aspects: (1) intermediate indicators, such as antigen DNA expression, APCs maturation rates, humoral and cellular immunity responses in serum, lymphoid organs or tissues, the T helper type 1 (Th1)/T helper type 2 (Th2) response bias, the memory T and B cells production and secretion levels of the related cytokines; 56,76,86 (2) comprehensive effects, such as higher animal survival rates, less weight loss and less tumor metastasis rates.…”

“…53 PEI-based vaccines with antigen peptides mainly follow the exogenous/class II pathway and stimulate the humoral immunity. 54 PEI-based DNA vaccines provide the opportunities to synthesize multiple antigens in APCs and stimulate effective cellular immunity and long-lasting memory immunity. However, most DNA is actually delivered to bystander cells (such as myocytes and fibroblasts).…”

Strategies for intranasal delivery of vaccines

“…SARS DNA vaccine Fig. 3 The structure of the lipid moieties used to enhance immunogenicity of weak antigens complexed with other cationic polymers effectively delivered the plasmid DNA to induce antigen-specific humoral and cellular immune responses [99]. PEI is of particular interest for intranasal delivery due to reported many-fold increase in gene transfer in the respiratory tract.…”

Enhancement of plasmid DNA immunogenicity with linear polyethylenimine

“…PEI is superior to other nonmicrobial transfection agents because of its ability to protect DNA from degradation [18], to escape intracellular endosomal lysis [19] and to efficiently deliver DNA into the nucleus of cells [20]. Formulation with PEI polymers has been employed in DNA-and siRNAbased immunotherapy against cancer [21,22] and in vaccination studies targeting different infectious agents [10,23,24].…”

“…PEI is superior to other nonmicrobial transfection agents because of its ability to protect DNA from degradation [18], to escape intracellular endosomal lysis [19] and to efficiently deliver DNA into the nucleus of cells [20]. Formulation with PEI polymers has been employed in DNA-and siRNAbased immunotherapy against cancer [21,22] and in vaccination studies targeting different infectious agents [10,23,24].In the present study, we have evaluated the physicochemical characteristics of a series of PEI polymers and have assessed associations between particular characteristics of these polymers and their ability to facilitate in vivo DNA expression and enhanced adaptive immune responses. Moreover, we have examined plasmid DNA constructs formulated with these various PEI polymers for their ability to generate immune responses under conditions that maximize the immunogenicity of these PEI-DNA complexes.…”