Author:
Chiale Carolina,Yarovinsky Timur O.,Mason Stephen W.,Madina Bhaskara R.,Menon Manisha,Krady Marie M.,Moshkani Safiehkhatoon,Chattopadhyay Pal Anasuya,Almassian Bijan,Rose John K.,Robek Michael D.,Nakaar Valerian
Abstract
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.
Funder
Connecticut Innovations
National Institute of Diabetes and Digestive and Kidney Diseases
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Subject
Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology
Cited by
4 articles.
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