Suschak John J, Golden Joseph W, Fitzpatrick Collin J, Shoemaker Charles J, Badger Catherine V, Schmaljohn Connie S, Garrison Aura R
Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
Diagnostics Systems Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
NPJ Vaccines. 2021 Mar 2;6(1):31. doi: 10.1038/s41541-021-00293-9.
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus that causes severe hemorrhagic fever disease in humans. Currently, no licensed CCHF vaccines exist, and the protective epitopes remain unclear. Previously, we tested a DNA vaccine expressing the M-segment glycoprotein precursor gene of the laboratory CCHFV strain IbAr 10200 (CCHFV-M). CCHFV-M provided >60% protection against homologous CCHFV-IbAr 10200 challenge in mice. Here, we report that increasing the dose of CCHFV-M provides complete protection from homologous CCHFV challenge in mice, and significant (80%) protection from challenge with the clinically relevant heterologous strain CCHFV-Afg09-2990. We also report complete protection from CCHFV-Afg09-2990 challenge following vaccination with a CCHFV-Afg09-2990 M-segment DNA vaccine (CCHFV-M). Finally, we show that the non-structural M-segment protein, GP38, influences CCHF vaccine immunogenicity and provides significant protection from homologous CCHFV challenge. Our results demonstrate that M-segment DNA vaccines elicit protective CCHF immunity and further illustrate the immunorelevance of GP38.
克里米亚-刚果出血热病毒（CCHFV）是一种蜱传病毒，可导致人类严重出血热疾病。目前，尚无获批的CCHF疫苗，其保护性表位仍不清楚。此前，我们测试了一种表达实验室CCHFV毒株IbAr 10200的M基因片段糖蛋白前体基因的DNA疫苗（CCHFV-M）。CCHFV-M在小鼠中对同源CCHFV-IbAr 10200攻击提供了>60%的保护。在此，我们报告增加CCHFV-M的剂量可使小鼠免受同源CCHFV攻击的完全保护，并对临床相关异源毒株CCHFV-Afg09-2990的攻击提供显著（80%）保护。我们还报告在用CCHFV-Afg09-2990 M基因片段DNA疫苗（CCHFV-M）接种后可完全保护免受CCHFV-Afg09-2990攻击。最后，我们表明非结构M基因片段蛋白GP38影响CCHF疫苗的免疫原性，并对同源CCHFV攻击提供显著保护。我们的结果表明，M基因片段DNA疫苗可引发保护性CCHF免疫，并进一步阐明了GP38的免疫相关性。
