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

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.

Understanding the Biology and Immune Pathogenesis of Chikungunya Virus Infection for Diagnostic and Vaccine Development

“…The expressed proteins subsequently form viral particles that are similar to intact virions because of their self-assembly capacity. However, VLPs are replication-incompetent because of the absence of genomic RNA and thus, have a better safety profile compared to LAV [ 211 ].…”

Evaluation of luciferase and prefusion-stabilized F protein from respiratory syncytial virus mRNA/LNPs in pre-clinical models using jet delivery compared to needle and syringe

“…One example is Tropis, which is commercially available and has been used to vaccinate over seven million people (mostly children) around the world ( [5] , [6] , [7] , [8] , [9] , PharmaJet personal communication). In general, there have been a number of vaccines evaluated using jet delivery, targeting protection from COVID, polio, rabies, hantaviruses, human papillomavirus (HPV), zika, HIV, chikungunya, dengue, influenza, and measles-mumps-rubella (MMR) [3] , [4] , [6] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] . These vaccines have been composed of mRNA or DNA that encode viral antigens, or attenuated or inactivated viruses [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] .…”

“…In general, there have been a number of vaccines evaluated using jet delivery, targeting protection from COVID, polio, rabies, hantaviruses, human papillomavirus (HPV), zika, HIV, chikungunya, dengue, influenza, and measles-mumps-rubella (MMR) [3] , [4] , [6] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] . These vaccines have been composed of mRNA or DNA that encode viral antigens, or attenuated or inactivated viruses [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] . A protamine-complexed mRNA vaccine for rabies was evaluated in a Phase I trial using jet delivery (Tropis (ID) and Stratis (IM)) and was found to be safe and effective when delivered via jet injection but not effective when needle/syringe was used [10] .…”