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Open AccessArticle

Modified Alphavirus-Vesiculovirus Hybrid Vaccine Vectors for Homologous Prime-Boost Immunotherapy of Chronic Hepatitis B

1
Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA
2
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA
3
CaroGen Corporation, Farmington, CT 06032, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Vaccines 2020, 8(2), 279; https://doi.org/10.3390/vaccines8020279
Received: 27 April 2020 / Revised: 29 May 2020 / Accepted: 31 May 2020 / Published: 5 June 2020
(This article belongs to the Section Therapeutic Vaccines and Antibody Therapeutics)
Virus-like vesicles (VLV) are hybrid vectors based on an evolved Semliki Forest virus (SFV) RNA replicon and the envelope glycoprotein (G) from vesicular stomatitis virus (VSV). Previously, we showed that VLV can be used to express protein antigens and generate protective antigen-specific CD8+ T cells. This report describes VLV vectors designed for enhanced protein expression and immunogenicity. Expressing hepatitis B virus (HBV) middle S antigen (MHBs) from VLV using a dual subgenomic promoter significantly increased MHBs-specific CD8+ T cell and antibody production in mice. Furthermore, envelope glycoprotein switch from VSV Indiana to the glycoprotein of Chandipura virus enabled prime-boost immunization and further increased responses to MHBs. Therapeutic efficacy was evaluated in a mouse model of chronic HBV infection initiated by HBV delivery with adeno-associated virus. Mice with lower or intermediate HBV antigen levels demonstrated a significant and sustained reduction of HBV replication following VLV prime-boost immunization. However, mice with higher HBV antigen levels showed no changes in HBV replication, emphasizing the importance of HBV antigenemia for implementing immunotherapies. This report highlights the potential of VLV dual promoter vectors to induce effective antigen-specific immune responses and informs the further development and evaluation of hybrid viral vaccine platforms for preventative and therapeutic purposes. View Full-Text
Keywords: hepatitis B virus; vesicular stomatitis virus; RNA replicon; immunotherapy hepatitis B virus; vesicular stomatitis virus; RNA replicon; immunotherapy
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Chiale, C.; Yarovinsky, T.O.; Mason, S.W.; Madina, B.R.; Menon, M.; Krady, M.M.; Moshkani, S.; Chattopadhyay Pal, A.; Almassian, B.; Rose, J.K.; Robek, M.D.; Nakaar, V. Modified Alphavirus-Vesiculovirus Hybrid Vaccine Vectors for Homologous Prime-Boost Immunotherapy of Chronic Hepatitis B. Vaccines 2020, 8, 279.

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