Type III interferon attenuates a vesicular stomatitis virus-based vaccine vector.

Area of Science:

• Virology
• Immunology
• Biotechnology

Background:

• Vesicular stomatitis virus (VSV) is a promising vaccine vector and oncolytic agent.
• Safety concerns limit the clinical application of VSV.
• Type III lambda interferon (IFN-λ) exhibits potent antiviral activity with a distinct receptor profile, primarily targeting epithelial cells.

Purpose of the Study:

• To investigate the impact of expressing IFN-λ from recombinant VSV on vector replication, spread, and immunogenicity.
• To evaluate IFN-λ as a strategy for attenuating VSV for improved safety in vaccine and oncolytic applications.

Main Methods:

• Recombinant VSV engineered to express IFN-λ was generated.
• VSV replication and spread were assessed in cell culture and in vivo (mouse model) after intranasal administration.
• Immunogenicity was evaluated by measuring CD8 T cell and antibody responses after a single immunization.

Main Results:

• IFN-λ expression significantly attenuated VSV replication in cell culture.
• In vivo, intranasal administration of IFN-λ-expressing VSV led to reduced viral replication in the lungs and limited systemic spread.
• Despite attenuation, the modified VSV vector effectively induced protective CD8 T cell and antibody responses.

Conclusions:

• IFN-λ expression serves as a novel and effective method for attenuating VSV.
• This attenuation strategy enhances the safety profile of VSV vectors without compromising their immunogenicity.
• IFN-λ-expressing VSV holds potential for developing safer and more effective viral vaccines and oncolytic agents.