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DNA vaccine cocktail expressing genotype A and C HBV surface and consensus core antigens generates robust cytotoxic and antibody responses in mice and Rhesus macaques

Cancer Gene Therapy volume 20, pages 652–662 (2013)Cite this article

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Abstract

There are well over a quarter of a billion chronic hepatitis B virus (HBV) carriers across the globe. Most carriers are at high risk for development of liver cirrhosis and subsequent progression to hepatocellular carcinoma. It is therefore imperative to develop new approaches for immunotherapy against this infection. Antibodies and cytotoxic T cells to different HBV antigens are believed to be important for reducing viral load and clearing HBV-infected cells from the liver. Some of the major challenges facing current vaccine candidates have been their inability to induce both humoral and cellular immunity to multiple antigenic targets and the induction of potent immune responses against the major genotypes of HBV. In this study, highly optimized synthetic DNA plasmids against the HBV consensus core (HBc) and surface (HBs) antigens genotypes A and C were developed and evaluated for their immune potential. These plasmids, which encode the most prevalent genotypes of the virus, were observed to individually induce binding antibodies to HBs antigens and drove robust cell-mediated immunity in animal models. Similar responses to both HBc and HBs antigens were observed when mice and non-human primates were inoculated with the HBc-HBs cocktails. In addition to the cytotoxic T lymphocyte activities exhibited by the immunized mice, the vaccine-induced responses were broadly distributed across multiple antigenic epitopes. These elements are believed to be important to develop an effective therapeutic vaccine. These data support further evaluation of multivalent synthetic plasmids as therapeutic HBV vaccines.

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Acknowledgements

This research was supported by a project grant (#350302) from the National Health and Medical Research Council (NHMRC) of Australia. DIG is supported by an NHMRC Senior Principal Research Fellowship (#1020770).

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA, Philadelphia, USA

    N Obeng-Adjei, N A Hutnick, J S Chu, D J F Myles & D B Weiner

  2. Inovio Pharmaceuticals Inc., PA, Blue Bell, USA

    J Yan, M P Morrow & N Y Sardesai

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  1. N Obeng-Adjei
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  2. N A Hutnick
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  3. J Yan
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Correspondence to D B Weiner.

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Competing interests

DBW has grant funding, participates in industry collaborations, has received speaking honoraria, and fees for consulting. This service includes serving on scientific review committees and advisory boards. Remuneration includes direct payments or stock or stock options and in the interest of disclosure therefore he notes potential conflicts associated with this work with Pfizer, Bristol Myers Squibb, Inovio, Merck, VGXI, Aldevron and possibly others. Licensing of technology from his laboratory has created over 100 jobs in the private sector in the biotech/pharma industry. The other UPenn authors declare no competing financial interests. JY, MPM, NYS are employees of Inovio Pharmaceuticals and as such receive salary and benefits from the company and hold stock or stock options in the company.

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Obeng-Adjei, N., Hutnick, N., Yan, J. et al. DNA vaccine cocktail expressing genotype A and C HBV surface and consensus core antigens generates robust cytotoxic and antibody responses in mice and Rhesus macaques. Cancer Gene Ther 20, 652–662 (2013). https://doi.org/10.1038/cgt.2013.65

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