PMID- 29137362 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231112 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 48 DP - 2017 Oct 13 TI - An optimized HMGB1 expressed by recombinant rabies virus enhances immunogenicity through activation of dendritic cells in mice. PG - 83539-83554 LID - 10.18632/oncotarget.18368 [doi] AB - Rabies remains an important public health threat, killing approximately 59,000 people worldwide annually, most of which are from the developing countries of Africa and Asia where dog rabies are endemic. Therefore, developing an affordable and efficacious vaccine for dog-mediated rabies control is needful in these countries. Our previous studies indicated that over-expression of granulocyte-macrophage colony stimulating factor (GM-CSF) or macrophage inflammatory protein-1 (MIP-1alpha or CCL3) by recombinant rabies virus (rRABV) could enhance the immunogenicity by activating dendritic cells (DCs). In this study, to further characterize the role of activating DCs in RABV immunogenicity, High mobility group box 1 (HMGB1), a highly conserved and non-histone chromosomal protein that can promote DCs maturation and activation, were investigated. The wild-type HMGB1 (HMGB1(wt)) and an optimized HMGB1 (HMGB1(mut)) were individually inserted into the genome of the rRABV strain LBNSE (designated as LBNSE-HMGB1(wt) and LBNSE-HMGB1(mut), respectively), and the effect of over-expression of HMGB1 on the immunogenicity of RABV was investigated. The results demonstrated that LBNSE-HMGB1(mut) could promote significantly more DCs activation, and the recruitment of follicular helper T, germinal center B and plasma cells in vaccinated mice than those immunized with LBNSE-HMGB1(wt) or parent virus LBNSE. Further investigations suggested that mice vaccinated with LBNSE-HMGB1(mut) produced significantly higher level of RABV-neutralizing antibodies and offered a better protection than those vaccinated with LBNSE or LBNSE-HMGB1(wt). Taken together, these data provides a better understanding of the mechanism for HMGB1 as a potential adjuvant in enhancing the immunogenicity of RABV, which would contribute to developing more-efficacious rabies vaccines. FAU - Wang, Zhao AU - Wang Z AD - State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China. AD - College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. FAU - Liang, Qian AU - Liang Q AD - State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China. AD - College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. FAU - Zhang, Yajing AU - Zhang Y AD - State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China. AD - College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. FAU - Yang, Jie AU - Yang J AD - State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China. AD - College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. FAU - Li, Mingming AU - Li M AD - State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China. AD - College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. FAU - Wang, Kunlun AU - Wang K AD - State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China. AD - College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. FAU - Cui, Min AU - Cui M AD - State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China. AD - College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. AD - Key Laboratory of Preventive Veterinary Medicine of Hubei Province, Huazhong Agricultural University, Wuhan, China. FAU - Chen, Huanchun AU - Chen H AD - State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China. AD - College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. AD - Key Laboratory of Preventive Veterinary Medicine of Hubei Province, Huazhong Agricultural University, Wuhan, China. FAU - Fu, Zhen F AU - Fu ZF AD - State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China. AD - College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. AD - Key Laboratory of Preventive Veterinary Medicine of Hubei Province, Huazhong Agricultural University, Wuhan, China. AD - Department of Pathology, University of Georgia, Athens, GA, USA. FAU - Zhao, Ling AU - Zhao L AD - State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China. AD - College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. AD - Key Laboratory of Preventive Veterinary Medicine of Hubei Province, Huazhong Agricultural University, Wuhan, China. FAU - Zhou, Ming AU - Zhou M AD - State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China. AD - College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. AD - Key Laboratory of Preventive Veterinary Medicine of Hubei Province, Huazhong Agricultural University, Wuhan, China. LA - eng PT - Journal Article DEP - 20170605 PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 PMC - PMC5663534 OTO - NOTNLM OT - HMGB1 OT - T follicular helper cells OT - dendritic cells OT - germinal center B cells OT - rabies virus COIS- CONFLICTS OF INTEREST No conflicts of interest was in this study. EDAT- 2017/11/16 06:00 MHDA- 2017/11/16 06:01 PMCR- 2017/10/13 CRDT- 2017/11/16 06:00 PHST- 2017/04/07 00:00 [received] PHST- 2017/05/02 00:00 [accepted] PHST- 2017/11/16 06:00 [entrez] PHST- 2017/11/16 06:00 [pubmed] PHST- 2017/11/16 06:01 [medline] PHST- 2017/10/13 00:00 [pmc-release] AID - 18368 [pii] AID - 10.18632/oncotarget.18368 [doi] PST - epublish SO - Oncotarget. 2017 Jun 5;8(48):83539-83554. doi: 10.18632/oncotarget.18368. eCollection 2017 Oct 13.