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.

Potent Inhibition of Late Stages of Hepadnavirus Replication by a Modified Cell Penetrating Peptide

“…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.…”

DNA vaccination of poultry: The current status in 2015

“…For example, between 60 and 90% of protection against experimental infections were achieved if plasmids encoding the S1, N and/or M proteins of the virus were inoculated [41]. In ducks, the most widely studied virus is duck hepatitis B virus (DHBV) as a model of chronic human hepatitis infection [42][43][44][45][46][47]. It has mainly been used to evaluate new treatments based on DNA vaccination (DNA vaccination alone or combined to lamivudine or entecavir).…”

“…Between 50 and 200 g of plasmid DNA was inoculated per injection in about 70% of the cases, whatever the bird species. In about 10% of the other studies, smaller amounts of plasmids were used if plasmid entry into cells at the injection point was forced [47], which is an interesting way to reduce the cost of the vaccination. On the other hand, few studies using over 500 g were published, though one used up to 10 mg per injection [5].…”

“…Electroporation forces plasmids to enter cells at the injection site thanks to an electric field. In poultry, it induced acute local inflammation of the injected muscle, recruited CD3 + T cells [47] and increased the intensity of both humoral and cellular immune responses [6,47]. Moreover, the quantity of plasmids needed was dramatically reduced (to 10 g in certain cases [47]).…”

“…In poultry, it induced acute local inflammation of the injected muscle, recruited CD3 + T cells [47] and increased the intensity of both humoral and cellular immune responses [6,47]. Moreover, the quantity of plasmids needed was dramatically reduced (to 10 g in certain cases [47]). Otherwise, ID injections of naked plasmid DNA were improved by administration with a gene gun, which propels DNA adsorbed onto gold beads onto the skin's surface [55,87,88].…”