A Therapeutic Hepatitis B Virus DNA Vaccine Induces Specific Immune Responses in Mice and Non-Human Primates
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 exhi...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/9/9/969 |
| _version_ | 1797516983980261376 |
|---|---|
| author | Dorien De Pooter Ellen Van Gulck Antony Chen Claire F. Evans Jean-Marc Neefs Helen Horton Daniel Boden |
| author_facet | Dorien De Pooter Ellen Van Gulck Antony Chen Claire F. Evans Jean-Marc Neefs Helen Horton Daniel Boden |
| author_sort | Dorien De Pooter |
| collection | DOAJ |
| description | 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<sup>+</sup> 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. |
| first_indexed | 2024-03-10T07:09:30Z |
| format | Article |
| id | doaj.art-47a9fd0208164534a56fcca1e29d82a0 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T07:09:30Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-47a9fd0208164534a56fcca1e29d82a02023-11-22T15:34:13ZengMDPI AGVaccines2076-393X2021-08-019996910.3390/vaccines9090969A Therapeutic Hepatitis B Virus DNA Vaccine Induces Specific Immune Responses in Mice and Non-Human PrimatesDorien De Pooter0Ellen Van Gulck1Antony Chen2Claire F. Evans3Jean-Marc Neefs4Helen Horton5Daniel Boden6Janssen Infectious Diseases, Janssen Research and Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, BelgiumJanssen Infectious Diseases, Janssen Research and Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, BelgiumJanssen Infectious Diseases, Janssen Research and Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, BelgiumIchor Medical Systems Inc., 6310 Nancy Ridge Drive, Suite 107, San Diego, CA 92121, USADiscovery Sciences, Janssen Research and Development, Division of Janssen Pharmaceutica NV, Turn-houtseweg 30, 2340 Beerse, BelgiumJanssen Infectious Diseases, Janssen Research and Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, BelgiumJanssen Infectious Diseases, Division of Janssen Pharmaceutica NV, 260 E. Grand Avenue, South San Francisco, CA 94080, USADespite 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<sup>+</sup> 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.https://www.mdpi.com/2076-393X/9/9/969therapeutic vaccinationhepatitis B surface antigen (HBsAg)hepatitis B virus (HBV) specific T-cellsHBV functional curenon-human primateelectroporation |
| spellingShingle | Dorien De Pooter Ellen Van Gulck Antony Chen Claire F. Evans Jean-Marc Neefs Helen Horton Daniel Boden A Therapeutic Hepatitis B Virus DNA Vaccine Induces Specific Immune Responses in Mice and Non-Human Primates Vaccines therapeutic vaccination hepatitis B surface antigen (HBsAg) hepatitis B virus (HBV) specific T-cells HBV functional cure non-human primate electroporation |
| title | A Therapeutic Hepatitis B Virus DNA Vaccine Induces Specific Immune Responses in Mice and Non-Human Primates |
| title_full | A Therapeutic Hepatitis B Virus DNA Vaccine Induces Specific Immune Responses in Mice and Non-Human Primates |
| title_fullStr | A Therapeutic Hepatitis B Virus DNA Vaccine Induces Specific Immune Responses in Mice and Non-Human Primates |
| title_full_unstemmed | A Therapeutic Hepatitis B Virus DNA Vaccine Induces Specific Immune Responses in Mice and Non-Human Primates |
| title_short | A Therapeutic Hepatitis B Virus DNA Vaccine Induces Specific Immune Responses in Mice and Non-Human Primates |
| title_sort | therapeutic hepatitis b virus dna vaccine induces specific immune responses in mice and non human primates |
| topic | therapeutic vaccination hepatitis B surface antigen (HBsAg) hepatitis B virus (HBV) specific T-cells HBV functional cure non-human primate electroporation |
| url | https://www.mdpi.com/2076-393X/9/9/969 |
| work_keys_str_mv | AT doriendepooter atherapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates AT ellenvangulck atherapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates AT antonychen atherapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates AT clairefevans atherapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates AT jeanmarcneefs atherapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates AT helenhorton atherapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates AT danielboden atherapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates AT doriendepooter therapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates AT ellenvangulck therapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates AT antonychen therapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates AT clairefevans therapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates AT jeanmarcneefs therapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates AT helenhorton therapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates AT danielboden therapeutichepatitisbvirusdnavaccineinducesspecificimmuneresponsesinmiceandnonhumanprimates |