Mutations that positively affect Bandavirus glycoprotein function on VSV vectored vaccines

Area of Science:

• Virology
• Vaccinology
• Molecular Biology

Background:

• Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV) are emerging tick-borne viruses causing severe illness and death.
• No FDA-approved vaccines or treatments are currently available for SFTSV and HRTV infections, highlighting an urgent need for preventative measures.

Purpose of the Study:

• To identify mutations that enhance the efficacy of recombinant vesicular stomatitis virus (rVSV) vaccine candidates for SFTSV and HRTV.
• To develop and evaluate a novel rVSV-based vaccine against HRTV.

Main Methods:

• Identified a noncanonical COPI binding motif in SFTSV glycoproteins and created a K1071A mutant.
• Created a homologous mutation (K1074A) in the rVSV-HRTV vaccine candidate.
• Assessed viral replication in vitro and in vivo, and evaluated neutralizing antibody responses and protective efficacy in mouse models.

Main Results:

• The K1071A mutation in SFTSV glycoproteins increased surface expression, virion incorporation, and rVSV-SFTSV replication.
• The homologous K1074A mutation enhanced rVSV-HRTV replication in vitro and in vivo.
• Vaccination with rVSV-HRTV K1074A induced potent neutralizing antibodies and provided protection against lethal challenge in mice.

Conclusions:

• A specific mutation targeting a COPI binding site significantly improves the efficacy of rVSV-SFTSV vaccine candidates.
• The study presents the first rVSV-based vaccine candidate for HRTV, demonstrating its potential for inducing protective immunity.
• These findings offer promising strategies for developing effective vaccines against SFTSV and HRTV, critical tick-borne pathogens.