Infectious enveloped RNA virus antigenic chimeras

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Sindbis virus is a widely studied alphavirus.
• Rift Valley fever virus causes significant disease in humans and animals.
• Developing novel vaccine strategies and targeted therapies is crucial for controlling viral infections.

Purpose of the Study:

• To construct infectious Sindbis virus chimeras displaying a heterologous viral epitope.
• To evaluate the immunogenicity and protective capacity of these chimeric viruses.
• To explore the potential of this method for vaccine development and targeted viral delivery.

Main Methods:

• Random insertion mutagenesis was employed to generate Sindbis virus structural protein chimeras.
• A neutralization epitope from Rift Valley fever virus was inserted into Sindbis virus glycoproteins (E2 and E3).
• Chimeric viruses were recovered and characterized for growth properties, epitope display, and immunogenicity in vivo.

Main Results:

• Permissive insertion sites were identified in the E2 and E3 glycoproteins, yielding chimeric viruses with parental growth properties.
• Chimeric viruses with insertions in E2 displayed the Rift Valley fever virus epitope on the virion surface.
• In vivo studies demonstrated that E2 chimeras elicited a partially protective immune response against Rift Valley fever virus infection.

Conclusions:

• Insertion of heterologous viral epitopes into Sindbis virus glycoproteins is feasible.
• Surface-expressed epitopes on chimeric viruses can induce a partial protective immune response.
• This strategy offers a potential platform for developing live-attenuated vaccines and for engineering virus tropism for targeted infections.