Enhanced magnitude and breadth of neutralizing humoral response to a DNA vaccine targeting the DHBV envelope protein delivered by in vivo electroporation

Université Lyon 1, France.
Virology (Impact Factor: 3.32). 03/2012; 425(1):61-9. DOI: 10.1016/j.virol.2012.01.001
Source: PubMed


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.

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Available from: Daniel Hartmann, Aug 20, 2014
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    • "Since HBV has an extremely narrow host range infecting only humans and chimpanzee, the closely related DHBV represents a reference and a very useful model to analyze gene function, viral replication and to evaluate novel antiviral strategies [27], [28], [29], [30], [31], [32], [33]. In search for new anti-HBV approaches, we have investigated in this model the ability of Peptide Nucleic Acids (PNAs) targeting the HBV signal ε to inhibit viral reverse transcription. "
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    • "Screening of induced antibodies in ducks for pre-S B-cell epitopes recognition The antibody response of individual duck sera to DHBV pre-S linear epitopes were analyzed using the PEPSCAN method (Khawaja et al., 2012). Briefly, a pepset of 77 9-mers peptides with an overlap of 7 amino acids, spanning the entire DHBV pre-S protein (residues 1–166) was synthesized by Mimotopes peptide company (UK) in the format Biotin-SGSG-PEPTIDE-amide. Each duck serum taken at week 40 was tested for peptide binding as described previously in details (Khawaja et al., 2012). "
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