Induction of gp120-specific protective immune responses by genetic vaccination with linear polyethylenimine–plasmid complex

Abstract

The induction of IFN-␥-secreting CD8+ T cells and neutralizing antibodies to HIV-1 are both key requirements for prevention of viral transmission and clearance of pathogenic HIV. Although DNA vaccination has been shown to induce both humoral and cellular immune responses against HIV antigens, the magnitude of the immune responses has always been disappointing. In this report, we analyze the ability of polyethylenimine (PEI)-DNA complex expressing an HIV-glycoprotein 120 (gp120) antigen (PEI-pgp120) to induce systemic CD8+ T cell and humoral responses to the gp120 antigen. The administration of PEI-plasmid complex resulted in rapid elevation of serum levels of IL-12 and IFN-␥. Furthermore, a single administration of PEI-pgp120 complex elicits a number of gp120-specific CD8+ T cells 20 times higher than that elicited by three intramuscular injections of naked DNA. Interestingly, we found that systemic vaccination with PEI-pgp120 induced protective immune responses against both systemic and mucosal challenges with a recombinant vaccinia virus expressing a gp120 antigen. The data also demonstrated that the depletion of macrophages with liposome-encapsulated clodronate completely abolished gp120-specific cellular response. Overall, our results showed that a single administration of PEI-pgp120 complexes, eliciting strong immune responses, is an effective vaccination approach to generate protection against systemic and mucosal viral infections.

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

“…Also the immunization enhanced antigen-specific IgA response in bronchoalveolar lavage fluid and B cell proliferation after in vitro re-stimulation with the spike protein. In Garzon's study, antigen-specific antibody and T cell responses have been dose-dependently increased in mice immunized with DNA vaccine up to 100 μg [20]. However, in our study each mouse was immunized with only 20 μg of DNA.…”

Systemic Delivery of DNA or siRNA Mediated by Linear Polyethylenimine (L-PEI) Does Not Induce an Inflammatory Response

“…Indeed it was reported in these studies that PEI/DNA immunization did not generate neutralizing antibodies against the delivery vector, even when injected repeatedly (61).…”

“…The induction of pro-inflammatory cytokines is lower with L-PEI/DNA complexes compared to cationic lipid-based systems, such as DOTMA:Chol (43) or DOTAP/Chol (as shown here). This decisive advantage over lipids and viruses added to a reasonable gene delivery efficiency may explain the recent developments of several PEI-based vaccines (19,20,60,61).…”

DNA Vaccines Approach: From Concepts to Applications

“…A study showed that this variability could have a direct effect on the transfection efficiency both in vitro and in vivo. The use of this polymer for DNA delivery in DNA-based immunotherapy or vaccination shows protective action by eliciting strong immune response [112]- [114].…”