Rayner Jonathan O, Kim Jin Hyun, Roberts Rosemary W, Wood Raphael Ryan, Fouty Brian, Solodushko Victor
Department of Microbiology and Immunology, University of South Alabama, Mobile, AL 36688, USA.
Departments of Internal Medicine and Pharmacology and Center for Lung Biology, University of South Alabama, Mobile, AL 36688, USA.
Vaccines (Basel). 2021 Apr 2;9(4):345. doi: 10.3390/vaccines9040345.
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.
基孔肯雅病毒(CHIKV)感染可导致慢性且使人衰弱的关节痛,影响着全球热带和亚热带地区的人类,但目前尚无预防感染的许可疫苗。DNA 启动的病毒样颗粒(VLP)疫苗是传统减毒活疫苗潜在更安全的替代品;然而,缺乏经过充分表征的免疫活性小鼠模型,该模型应适当纳入雄性和雌性动物,用于这些以及其他疫苗平台的临床前评估。利用经过基因工程改造以表达据报道可增强 CHIKV 在小鼠中毒力的突变的病毒株,评估了雄性和雌性免疫活性小鼠的感染情况,并利用所得模型评估候选 DNA 启动的 CHIKV VLP 疫苗的功效。结果表明,与减毒活 CHIKV 疫苗相比,DNA 启动的 VLP 疫苗具有潜在效用,并确定了病毒 RNA 载量的性别差异,这会影响疫苗功效的解读,可能对未来 CHIKV 疫苗的开发具有重要意义。