期刊
HUMAN GENE THERAPY
卷 32, 期 21-22, 页码 1360-1369出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2021.037
关键词
electrotransfer; DNA vaccine; gene delivery; electroporation; Hepatitis B; multielectrode array
资金
- National Institutes of Health NIBIB [R01 EB018956]
An estimated 350 million people worldwide are living with chronic Hepatitis B virus, with preventative HBV vaccination in infants reducing disease burden to some extent. However, vulnerable populations in endemic regions are still at risk of infection. Gene electrotransfer (GET) combined with moderate heating can achieve higher levels of gene expression than GET alone, potentially serving as a strong immune response inducing platform.
An estimated 350 million people are living with chronic Hepatitis B virus (HBV) worldwide. Preventative HBV vaccination in infants has reduced the disease burden; however, insufficient immunization programs and access obstacles leave vulnerable populations at risk for infection in endemic regions. Gene electrotransfer (GET) using a noninvasive multielectrode array (MEA) provides an alternative platform for DNA vaccination in the skin. DNA vaccines are nonlive and nonreplicating and temperature stable unlike their counterparts. In addition, their simple engineering allows them to be manufactured quickly at a low cost. In the current work, we present the combination of GET and moderate heating for delivery of a DNA vaccine against HBV. Our laboratory has previously shown the synergy between moderate tissue preheating at 43 degrees C and GET with the MEA as a means to reduce both the applied voltage and pulse number to achieve similar if not higher gene expression than GET alone. In this study, we expand upon this work, by optimizing the plasmid dose to achieve the highest level of expression. Using the reporter gene luciferase, we found that an intradermal injection of 100 mu L at 1 mg/mL induced the highest expression levels across all tested GET conditions. We then evaluated our moderate heat-assisted GET platform for the intradermal delivery of a plasmid encoding Hepatitis B surface antigen (pHBsAg) via a prime and prime plus boost vaccination protocol. At 18 weeks, following the prime plus boost protocol, we observed that a high-voltage low-pulse GET condition with moderate heating (45 V 36 p+heat) generated antibodies against Hepatitis B surface antigen (HBsAb) at peak measuring 230-fold over injection of plasmid DNA alone with moderate heating. HBsAbs remained robust over the 30-week observation period. These data suggest that moderate heat-assisted GET has the potential to induce strong immune responses, an attractive feature for development of an alternative vaccine delivery platform.
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