Vaccination with single plasmid DNA encoding IL-12 and antigens of severe fever with thrombocytopenia syndrome virus elicits complete protection in IFNAR knockout mice

Jun-Gu Kang; Kyeongseok Jeon; Hooncheol Choi; Yuri Kim; Hong-Il Kim; Hyo-Jin Ro; Yong Bok Seo; Jua Shin; Junho Chung; Yoon Kyung Jeon; Yang Soo Kim; Keun Hwa Lee; Nam-Hyuk Cho

To assess the protective efficacy of the DNA vaccine, groups of mice were immunized with . CC-BY 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/787879 doi: bioRxiv preprint 17 386 mock vector, pSFTSV, or pSFTSV-IL12 three times and then subcutaneously challenged 387 with a lethal dose (10 5 FFU/mouse) of SFTSV (Fig. 4) . All the mock-immunized mice 388 expired by 5 d after SFTSV infection. In contrast, all the mice immunized with pSFTSV-IL12 389 were protected from lethal viral challenge, and 40% (2 of 5) of mice vaccinated with pSFTSV 390 survived (Fig. 4A) . Consistently, pSFTSV-IL12-vaccinated animals lost weight until 4 d after vaccinated mice (mean ± S.D. = 4.2 × 10 6 ± 4.6 × 10 6 ) were approximately five and fifty 402 times lower than those of pSFTSV-vaccinated mice (mean ± S.D. = 2.1 × 10 7 ± 1.7 × 10 7 ) 403 and vector-immunized mice (mean ± S.D. = 2.0 × 10 8 ± 1.9 × 10 8 ) at 4 d, respectively. Given that immunization with Gn-Fc and Gc-Fc proteins can induce specific antibodies in 478 IFNAR KO mice (Fig. 5) Flt3L can significantly enhance CD8 T cell responses when fused with a target antigen and 484 promote persistent maintenance of antigen-specific CD8 T cells in vivo [16, 29] . In this study, 485 we also observed significant enhancement of Gn and NP-specific CD8 T cell responses, as 486 well as CD4 T cells, in the presence of IL-12 expression ( Fig. 3B and C) , which correlated