Abstract
Despite the availability of an effective prophylactic vaccine for more than 30 years, nearly 300 million people worldwide are chronically infected with the hepatitis B virus (HBV), leading to 1 death every 30 s mainly from viral hepatitis-related cirrhosis and liver cancer. Chronic HBV patients exhibit weak, transient, or dysfunctional CD8+ T-cell responses to HBV, which contrasts with high CD8+ T-cell responses seen for resolvers of acute HBV infection. Therefore, a therapeutic DNA vaccine was designed, expressing both HBV core and polymerase proteins, and was sequence optimized to ensure high protein expression and secretion. Although the vaccine, administered intramuscularly via electroporation, had no effect on plasma viral parameters in a mouse model of persistent HBV infection, it did induce robust HBV-specific immune responses in healthy and adeno-associated hepatitis B virus (AAV-HBV) infected mice as well as in healthy non-human primates.
Highlights
Approximately 300 million people are chronically infected with the hepatitis B virus (HBV) [1,2], even though a highly effective prophylactic vaccine against HBV has been available since 1982 [3]
The patients who resolve their HBV infection have readily detectable ex vivo HBV-specific CD4+ and CD8+ T-cell responses, while such responses are less frequent and functionally impaired in chronic HBV-infected individuals [10]. These findings suggest that therapeutic vaccination should induce HBV-specific CD4+ and CD8+ T-cell responses that mimic those seen in resolvers
Of 19 into HEK293T cells, the Woodchuck post-transcriptional regulatory element (WPRE) inclusion only slightly increased cellular expression8over parental core protein (Core) plasmid, whereas it had no effect on secreted Core protein yield (Figure 1A)
Summary
Dorien De Pooter 1, *, Ellen Van Gulck 1 , Antony Chen 1 , Claire F.
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