A Therapeutic Hepatitis B Virus DNA Vaccine Induces Specific Immune Responses in Mice and Non-Human Primates

• Published in: Vaccines (Basel) Vol. 9; no. 9; p. 969
• Main Authors: De Pooter, Dorien, Van Gulck, Ellen, Chen, Antony, Evans, Claire F., Neefs, Jean-Marc, Horton, Helen, Boden, Daniel
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 29.08.2021; MDPI
• Subjects: Antibiotics; Antigens; CD8 antigen; Cirrhosis; Cloning; Cytomegalovirus; Deoxyribonucleic acid; DNA; DNA vaccines; DNA viruses; Electroporation; Genotype & phenotype; HBV functional cure; Hepatitis; Hepatitis B; hepatitis B surface antigen (HBsAg); hepatitis B virus (HBV) specific T-cells; Immune response; Infections; Liver cancer; Liver cirrhosis; Lymphocytes T; Mutation; non-human primate; Plasmids; Primates; Protein expression; Proteins; Resolvers; therapeutic vaccination; Vaccines; Southeast Asia; Asia; United States > US; Australasia; Oceania
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines9090969

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.