title: Enhanced magnitude and breadth of neutralizing humoral response to a DNA vaccine targeting the DHBV envelope protein delivered by in vivo electroporation.
abstract: We explored in the duck hepatitis B virus (DHBV) model the impact of electroporation (EP)-mediated DNA vaccine delivery on the neutralizing humoral response to viral preS/S large envelope protein. EP enhanced the kinetics and magnitude of anti-preS response compared to the standard needle DNA injection (SI). Importantly, EP dramatically enhanced the neutralizing potency of the humoral response, since antibodies induced by low DNA dose (10 μg) were able to highly neutralize DHBV and to recognize ten antigenic regions, including four neutralization epitopes. Whereas, SI-induced antibodies by the same low DNA dose were not neutralizing and the epitope pattern was extremely narrow, since it was limited to only one epitope. Thus, EP-based delivery was able to improve the dose efficiency of DNA vaccine and to maintain a highly neutralizing, multi-specific B-cell response, suggesting that it may be an effective approach for chronic hepatitis B therapy at clinically feasible DNA dose.
authors.affiliation: Université Lyon 1, France.
authors.forename: Ghada
authors.initials: G
authors.lastname: Khawaja
authors.forename: Thierry
authors.initials: T
authors.lastname: Buronfosse
authors.forename: Catherine
authors.initials: C
authors.lastname: Jamard
authors.forename: Sylviane
authors.initials: S
authors.lastname: Guerret
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.forename: Alain
authors.initials: A
authors.lastname: Luxembourg
authors.forename: Drew
authors.initials: D
authors.lastname: Hannaman
authors.forename: Claire
authors.initials: C
authors.lastname: Evans
authors.forename: Daniel
authors.initials: D
authors.lastname: Hartmann
authors.forename: Lucyna
authors.initials: L
authors.lastname: Cova
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D016503:Drug Delivery Systems; D004372:Ducks; D018274:Electroporation / Q000379:methods*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018347:Hepadnaviridae Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D006510:Hepatitis B Antibodies / Q000097:blood; D015611:Hepatitis B Virus, Duck / Q000235:genetics / Q000276:immunology*; D006524:Hepatitis, Viral, Animal / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D018985:Epitopes, B-Lymphocyte; D006510:Hepatitis B Antibodies; D011498:Protein Precursors; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins