In the realm of viral vector-based therapeutics, the utilization of recombinant vesicular stomatitis virus (rVSV) pseudotyped with Marburg virus glycoprotein (MARV GP) holds significant promise for targeted gene delivery and immunotherapy against Marburg virus infection. This study presents the development and comprehensive characterization of AffiVIR®, a novel rVSV pseudotyped with MARV GP, focusing on its molecular engineering, in vitro functionality, and potential applications in preclinical and clinical settings.
Marburg virus (MARV) is a highly pathogenic virus belonging to the family Filoviridae, notorious for causing severe hemorrhagic fever with high mortality rates in humans. Despite advancements in antiviral therapies and vaccines, the absence of specific treatments for Marburg virus infection underscores the urgent need for innovative therapeutic approaches. Viral vectors, particularly recombinant vesicular stomatitis virus (rVSV), have emerged as promising platforms for gene delivery and immunotherapy due to their high transduction efficiency and safety profiles. Pseudotyping rVSV with MARV glycoprotein (GP) further enhances its specificity and efficacy in targeting MARV-infected cells.
Methods
The development of AffiVIR® involved the generation of a recombinant rVSV backbone expressing essential viral genes and harboring a modified MARV GP gene. Molecular engineering techniques, including reverse genetics and site-directed mutagenesis, were employed to optimize the expression and incorporation of MARV GP onto the rVSV envelope. The resultant AffiVIR® vector was characterized using a range of in vitro assays to assess its infectivity, tropism, stability, and immunogenicity.
Results
AffiVIR® demonstrated robust infectivity in a variety of cell lines, including MARV-permissive cells, indicating its broad tropism and efficacy in targeting MARV-infected cells. Immunofluorescence and electron microscopy analyses confirmed the surface expression and incorporation of MARV GP onto AffiVIR® particles, validating the pseudotyping strategy. Furthermore, in vitro cytotoxicity assays revealed negligible off-target effects of AffiVIR®, highlighting its safety profile for therapeutic applications. Importantly, AffiVIR® induced potent humoral and cellular immune responses against MARV antigens in vitro, suggesting its potential as a vaccine candidate against Marburg virus infection.
AffiVIR® represents a promising therapeutic platform for targeted gene delivery and immunotherapy against Marburg virus infection. Its successful development and characterization underscore its potential for translation into preclinical and clinical studies, offering new avenues for combating emerging viral threats. Future investigations will focus on evaluating the efficacy and safety of AffiVIR® in relevant animal models and advancing its clinical development as a novel therapeutic intervention for Marburg virus infection.