Evaluation of DNA-Launched Virus-Like Particle Vaccines in an Immune Competent Mouse Model of Chikungunya Virus Infection

Jonathan O. Rayner, Department of Microbiology and Immunology, University of South Alabama, Mobile, AL 36688, USA.
Jin Hyun Kim, Department of Microbiology and Immunology, University of South Alabama, Mobile, AL 36688, USA.
Rosemary W. Roberts, Department of Microbiology and Immunology, University of South Alabama, Mobile, AL 36688, USA.
Raphael Ryan Wood, Department of Microbiology and Immunology, University of South Alabama, Mobile, AL 36688, USA.
Brian Fouty, Departments of Internal Medicine and Pharmacology and Center for Lung Biology, University of South Alabama, Mobile, AL 36688, USA.
Victor Solodushko, Department of Pharmacology and Center for Lung Biology, University of South Alabama, Mobile, AL 36688, USA.

Abstract

Chikungunya virus (CHIKV) infection can result in chronic and debilitating arthralgia affecting humans in tropical and subtropical regions around the world, yet there are no licensed vaccines to prevent infection. DNA launched virus like particle (VLP) vaccines represent a potentially safer alternative to traditional live-attenuated vaccines; however, fully characterized immunocompetent mouse models which appropriately include both male and female animals for preclinical evaluation of these, and other, vaccine platforms are lacking. Utilizing virus stocks engineered to express mutations reported to enhance CHIKV virulence in mice, infection of male and female immunocompetent mice was evaluated, and the resulting model utilized to assess the efficacy of candidate DNA launched CHIKV VLP vaccines. Results demonstrate the potential utility of DNA launched VLP vaccines in comparison to a live attenuated CHIKV vaccine and identify gender differences in viral RNA loads that impact interpretation of vaccine efficacy and may have important implications for future CHIKV vaccine development.