Electroporation at Low Voltages Enables DNA Vaccine to Provide Protection against a Lethal H5N1 Avian Influenza Virus Challenge in Mice

Abstract

Objective: Electroporation has been proved to enhance the efficacy of intramuscular delivery of DNA. However, the process of electroporation causes pain and discomfort to the patient receiving the treatment. Higher the electroporation voltages inflict greater pain, and this limits the circumstances in which the technique can be used clinically. The voltages generally used for electroporation in animals range from 100 to 1,200 V/cm. We studied the effect of DNA vaccination when electroporation was performed at lower voltages. Methods: BALB/c mice were immunized twice by electroporation, at a 3-week interval, with H5N1 virus hemagglutinin (HA) DNA. One week after the booster had been given, the mice were challenged with a lethal dose of mouse-adapted H5N1 virus. The immune effects of HA DNA were evaluated by the survival rate, lung virus titer, bodyweight change and antibody titer of the mice. Results: The higher the voltage used, the more able were the mice to survive the challenge. However, a significant degree of protection could also be achieved with a voltage as low as 5 V. When electroporation was performed at a voltage of 10 V, an immunization amount of 5 µg is enough for HA DNA to provide effective protection. Conclusion: Low-voltage electroporation can induce immunity and protect mice effectively. There is, therefore, the potential to reduce the voltages currently used for DNA electroporation.

Protective Efficacy and Immunogenicity of a Combinatory DNA Vaccine against Influenza A Virus and the Respiratory Syncytial Virus

“…Additionally our experiments demonstrate that two immunizations even with a low dose of 2 µg per plasmid were sufficient to provide protective antibody responses. This confirms the finding of Zhou et al , who used a comparable vaccination protocol with either 5 µg or 30 µg of an H5 expressing plasmid and could show that the higher dose induced strong antibody responses already after the initial priming, whereas a second shot was needed for the lower dose [36]. In our previous work, we found the neutralizing antibody titers induced by this vaccination protocol to be comparable to those in humans after a single vaccination with a commercial H1N1(2009) vaccine (Pandemrix©) ([5] and unpublished data).…”

DNA vaccines encoding DEC205‐targeted antigens: immunity or tolerance?

“…Secreted antigens can be easily taken up by dendritic cells (DCs), which subsequently present them to T cells in the lymphatic tissues. The immunogenicity and efficacy of DNA vaccines were dramatically improved by using in vivo electroporation . The short electric pulses have been shown to enhance the DNA uptake and induce inflammation at the injection site, which leads to the recruitment of immune cells …”

“…The immunogenicity and efficacy of DNA vaccines were dramatically improved by using in vivo electroporation. [9][10][11] The short electric pulses have been shown to enhance the DNA uptake and induce inflammation at the injection site, which leads to the recruitment of immune cells. 12,13 Dendritic cells take up pathogens from the periphery by phagocytosis or receptor-mediated endocytosis.…”

Improving the reach of vaccines to low-resource regions, with a needle-free vaccine delivery device and long-term thermostabilization

“…Also, biolistic delivery is hindered by the high sensitivity of the ballistic penetration process to obvious and subtle variation in skin properties [16] and high cell death [17]. The electroporation process causes pain and discomfort to patients [18][19][20].…”