Intranasal delivery of plasmids expressing bovine herpesvirus 1 gB/gC/gD proteins by polyethyleneimine magnetic beads activates long-term immune responses in mice

Abstract

Background DNA vaccine is one of the research hotspots in veterinary vaccine development. Several advantages, such as cost-effectiveness, ease of design and production, good biocompatibility of plasmid DNA, attractive biosafety, and DNA stability, are found in DNA vaccines. Methods In this study, the plasmids expressing bovine herpesvirus 1 (BoHV-1) gB, gC, and gD proteins were mixed at the same mass ratio and adsorbed polyethyleneimine (PEI) magnetic beads with a diameter of 50 nm. Further, the plasmid and PEI magnetic bead polymers were packaged into double carboxyl polyethylene glycol (PEG) 600 to use as a DNA vaccine. The prepared DNA vaccine was employed to vaccinate mice via the intranasal route. The immune responses were evaluated in mice after vaccination. Results The expression of viral proteins could be largely detected in the lung and rarely in the spleen of mice subjected to a vaccination. The examination of biochemical indicators, anal temperature, and histology indicated that the DNA vaccine was safe in vivo. However, short-time toxicity was observed. The total antibody detected with ELISA in vaccinated mice showed a higher level than PBS, DNA, PEI + DNA, and PBS groups. The antibody level was significantly elevated at the 15th week and started to decrease since the 17th week. The neutralizing antibody titer was significantly higher in DNA vaccine than naked DNA vaccinated animals. The total IgA level was much greater in the DNA vaccine group compared to other component vaccinated groups. The examination of cellular cytokines and the percentage of CD4/CD8 indicated that the prepared DNA vaccine induced a strong cellular immunity. Conclusion The mixed application of plasmids expressing BoHV-1 gB/gC/gD proteins by nano-carrier through intranasal route could effectively activate long-term humoral, cellular, and mucosal immune responses at high levels in mice. These data indicate PEI magnetic beads combining with PEG600 are an efficient vector for plasmid DNA to deliver intranasally as a DNA vaccine candidate.

The menace of severe adverse events and deaths associated with viral gene therapy and its potential solution

“…497,498 Magnetic NPs are also utilized for DNA delivery as a part of more complex delivery systems that also contain cationic polymers. 380 In a recent study in the murine model, Liu et al 499 intranasally delivered pDNA encoding bovine herpesvirus-1 proteins with the help of PEG-coated, PEI-conjugated magnetic nanobeads. The researchers observed strong cellular immunity and approximately threefold increase in nAb levels compared to nasally delivered naked pDNA.…”

Magnetic Nanoparticles for Nucleic Acid Delivery: Magnetofection, Gene Therapy and Vaccines

“…In this group, it is possible to find a vaccine development for bovine herpesvirus type 1 (BoHV-1) which is one of the causative pathogens for the bovine respiratory syndrome [114]. The authors propose an alternative route of immunization, intranasal, due to low mucosal immunity of inactivated and gene-deleted vaccines after muscle injection for commercial formulations.…”