PMID- 30978448 OWN - NLM STAT- MEDLINE DCOM- 20190716 LR - 20190716 IS - 1095-9947 (Electronic) IS - 1050-4648 (Linking) VI - 89 DP - 2019 Jun TI - Effect of CXCL12-expressing viral hemorrhagic septicemia virus replicon particles on leukocytes migration and vaccine efficacy in olive flounder (Paralichthys olivaceus). PG - 378-383 LID - S1050-4648(19)30256-6 [pii] LID - 10.1016/j.fsi.2019.04.018 [doi] AB - Viral replicon particles are single-cycle viruses defective for function(s) needed for viral replication, which allow them to be recognized as a safer form for the vaccination of animals compared to attenuated live viruses. However, deletion of genes that are critical for the induction of protective immunity can diminish the vaccine potential of viral replicon particles. Therefore, the manipulation of viral replicon particles to produce a molecular adjuvant can be a way to increase immunogenicity of vaccines based on viral replicon particles. Chemokines are a class of chemotactic cytokines that control the migration of diverse cells of vertebrates. CXC chemokine ligand 12 (CXCL12) binds to a receptor CXCR4, and CXCL12-CXCR4 signaling plays an important role in the migration of hematopoietic cells during embryogenesis and the attraction of leukocytes. In the present study, to evaluate the possible use of CXCL12 as a molecular adjuvant for an rVHSV-DeltaG vaccine and to know differences between CXCL12a and CXCL12b in the adjuvant ability, we rescued VHSV replicon particles that are expressing olive flounder CXCL12a, CXCL12b, or eGFP (rVHSV-DeltaG-CXCL12a, rVHSV-DeltaG-CXCL12b, or rVHSV-DeltaG-eGFP), and compared the ability to attract olive flounder leucocytes and to induce protection against a VHSV challenge. In the leukocytes migration assay, supernatants collected from cells infected with rVHSV-DeltaG-CXCL12a and rVHSV-DeltaG-CXCL12b showed significantly higher ability to attract olive flounder leukocytes than the supernatant of cells infected with rVHSV-DeltaG-eGFP. Moreover, the significantly higher number of leukocytes were attracted to rVHSV-CXCL12a supernatant compared to rVHSV-CXCL12b supernatant, suggesting that CXCL12a would be more appropriate for the induction of immunity than CXCL12b in olive flounder. In the immunization experiment, olive flounder immunized with rVHSV-DeltaG-CXCL12a showed significantly higher survival rate than fish immunized with rVHSV-DeltaG-CXCL12b or rVHSV-DeltaG-eGFP. In addition, fish immunized with rVHSV-DeltaG-CXCL12a showed the highest serum neutralization activity. These results suggest the availability of CXCL12a for a molecular adjuvant of vaccines based on VHSV replicon particles. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Choi, Myoung Gwang AU - Choi MG AD - Department of Aquatic Life Medicine, Pukyong National University, Busan, 48513, South Korea. FAU - Kim, Min Sun AU - Kim MS AD - Department of Integrative Bio-industrial Engineering, Sejong University, Seoul, 05006, South Korea. FAU - Choi, Tae-Jin AU - Choi TJ AD - Department of Microbiology, Pukyong National University, Busan, 48513, South Korea. FAU - Kim, Ki Hong AU - Kim KH AD - Department of Aquatic Life Medicine, Pukyong National University, Busan, 48513, South Korea. Electronic address: khkim@pknu.ac.kr. LA - eng PT - Journal Article DEP - 20190409 PL - England TA - Fish Shellfish Immunol JT - Fish & shellfish immunology JID - 9505220 RN - 0 (Chemokine CXCL12) RN - 0 (Fish Proteins) RN - 0 (Viral Vaccines) SB - IM MH - Animals MH - Cell Movement MH - Chemokine CXCL12/*immunology MH - Fish Diseases/immunology/*prevention & control/virology MH - Fish Proteins/*immunology MH - Flatfishes/*immunology MH - Hemorrhagic Septicemia, Viral/immunology/*prevention & control/virology MH - Leukocytes/immunology/physiology MH - Novirhabdovirus/*immunology MH - Random Allocation MH - Replicon/immunology MH - Viral Vaccines/*administration & dosage/immunology OTO - NOTNLM OT - CXCL12a OT - Molecular adjuvant OT - VHSV replicon particle OT - Vaccine EDAT- 2019/04/13 06:00 MHDA- 2019/07/17 06:00 CRDT- 2019/04/13 06:00 PHST- 2018/11/20 00:00 [received] PHST- 2019/03/26 00:00 [revised] PHST- 2019/04/05 00:00 [accepted] PHST- 2019/04/13 06:00 [pubmed] PHST- 2019/07/17 06:00 [medline] PHST- 2019/04/13 06:00 [entrez] AID - S1050-4648(19)30256-6 [pii] AID - 10.1016/j.fsi.2019.04.018 [doi] PST - ppublish SO - Fish Shellfish Immunol. 2019 Jun;89:378-383. doi: 10.1016/j.fsi.2019.04.018. Epub 2019 Apr 9.