Synthetic DNA immunogen encoding hepatitis B core antigen drives immune response in liver

Abstract

The prevalence of hepatitis B virus (HBV) infection in Asia and sub-Sahara Africa is alarming. With quarter of a billion people chronically infected worldwide and at risk of developing liver cancer, the need for a prophylactic or therapeutic vaccination approach that can effectively induce protective responses against the different genotypes of HBV is more important than ever. Such a strategy will require both the induction of a strong antigen-specific immune response and the subsequent deployment of immune response towards the liver. Here, we assessed the ability of a synthetic DNA vaccine encoding a recombinant consensus plasmid from genotype A through E of the HBcAg, to drive immunity in the liver. Intramuscular vaccination induced both strong antigen-specific T cell and high titer antibody responses systematically and in the liver. Furthermore, immunized mice showed strong cytotoxic responses that eliminate adoptively transferred HBV-coated target cells. Importantly, vaccine-induced immune responses provided protection from HBcAg plasmid-base liver transfection in a hydrodynamic liver transfection model. These data provide important insight into the generation of peripheral immune responses that are recruited to the liver- an approach that can be beneficial in the search for vaccines or immune-therapies to liver disease.

Functional Aspects of Intrahepatic Hepatitis B Virus-specific T Cells Induced by Therapeutic DNA Vaccination

“…Several studies have investigated HBcAg as a potential genetic- or protein-based vaccine. 32 , 36 , 37 A key feature needed in an HBcAg-specific therapeutic vaccine for chronic HBV is the ability to induce strong and durable T-cell responses. To optimize the immunogenicity of DNA vaccines, several approaches have been evaluated.…”

Humoral Immune Response in Mice Elicited by Combined Yeast-Derived Hepatitis B Virus Core, Surface, and Mosaic Surface Antigens

“…HBcAg induces a strong antibody response during HBV infection [18] and the recombinant form, derived from Escherichia coli , has been shown to provide substantial protection in chimpanzees [22,37,38] . In the animals in which the protection was not complete, the infection was mild, as indicated by the low and shortlived HBsAg titer [22] , and when delivered as a DNA vaccine in mice it has elicited strong T cell and high titer antibody responses [39] . In our study, the yeast-derived HBcAg also induced a strong antibody response, both individually and in combination with the other antigens.…”

Chronic hepatitis B: A wave of new therapies on the horizon

“…INO-1800 is a recombinant DNA vaccine from Inovio that encodes consensus sequence of HBV core antigen, which has induced antigen-specific strong T-cell responses and high antibody titers in preclinical trials (Obeng-Adjei et al, 2012). The vaccine also demonstrated strong cytotoxic T-cell response to kill target cells without causing considerable liver injury (Obeng-Adjei et al, 2012).…”

“…The vaccine also demonstrated strong cytotoxic T-cell response to kill target cells without causing considerable liver injury (Obeng-Adjei et al, 2012). The company has just initiated Phase1 trials for the vaccine (Inovio, 2015)…”