PMID- 32199211 OWN - NLM STAT- MEDLINE DCOM- 20200713 LR - 20200713 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 121 DP - 2020 May TI - Enhanced efficacy of a multi-epitope vaccine for type A and O foot‑and-mouth disease virus by fusing multiple epitopes with Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA), a novel TLR4 agonist. PG - 118-126 LID - S0161-5890(19)30692-3 [pii] LID - 10.1016/j.molimm.2020.02.018 [doi] AB - Foot-and-mouth disease (FMD) is an acute, severe, and highly contagious disease that affects cloven-hoofed animals and can lead to serious economic losses and social effects. Therefore, a safe and effective subunit vaccine is required to prevent and control FMD. Dendritic cells (DCs) are a type of professional antigen presenting cell (APC). Immature DCs are typically stimulated by various adjuvants via immune receptors (e.g., toll-like receptor 4 [TLR4]), which activate DCs to induce their maturation. TLR4 has been well-established to induce both innate and adaptive immune responses to various external microbial or internal damage-related molecular patterns. In this study, the multi-epitope immunogen, HAO, of foot-and-mouth disease virus (FMDV) serotypes A and O was fused with the recombinant protein, heparin-binding hemagglutinin (HBHA), a novel TLR4 agonist, to obtain a new recombinant fusion protein, termed HAO-HBHA. HAO-HBHA was found to be highly efficient at activating murine DCs by the TLR4 pathway, both in vitro and in vivo. HAO-HBHA elicited strong specific humoral immune responses detected with an ELISA and virus neutralizing antibody test (VNT). HAO-HBHA also elevated the cellular immune responses, as indicated by intracellular cytokine (e.g., IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10, and IL-12p70) expression in Th1 and Th2 cells. As a TLR4 agonist, HBHA has significant advantages for enhancing the immune efficacy of a FMDV serotype A and O bivalent multi-epitope vaccine. These findings provide a novel strategy for the development of a safe and effective multi-epitope vaccine candidate against FMDV and further extends the application of TLR agonist-based vaccine platforms. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Lei, Yao AU - Lei Y AD - State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu Province, 225009, China. FAU - Shao, Junjun AU - Shao J AD - State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu Province, 225009, China. FAU - Ma, Feifei AU - Ma F AD - State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, China. FAU - Lei, Chenglin AU - Lei C AD - State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, China. FAU - Chang, Huiyun AU - Chang H AD - State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu Province, 225009, China. Electronic address: changhuiyun@caas.cn. FAU - Zhang, Yongguang AU - Zhang Y AD - State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu Province, 225009, China. Electronic address: zhangyongguang@caas.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200318 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (Epitopes, B-Lymphocyte) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (Lectins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Toll-Like Receptor 4) RN - 0 (Vaccines, Subunit) RN - 0 (Viral Vaccines) RN - 0 (heparin-binding hemagglutinin) SB - IM MH - Adjuvants, Immunologic/pharmacology MH - Animals MH - Antibodies, Neutralizing/blood/immunology MH - Antibodies, Viral/blood/immunology MH - Dendritic Cells/immunology MH - Epitopes, B-Lymphocyte/genetics/immunology MH - Epitopes, T-Lymphocyte/genetics/immunology MH - Female MH - Foot-and-Mouth Disease/blood/immunology/*prevention & control/virology MH - Foot-and-Mouth Disease Virus/genetics/*immunology MH - Immunity, Cellular MH - Immunogenicity, Vaccine MH - Lectins/immunology/*pharmacology MH - Mice MH - Mycobacterium tuberculosis/immunology MH - Recombinant Fusion Proteins/administration & dosage/genetics/immunology MH - Serogroup MH - Toll-Like Receptor 4/agonists/immunology MH - Vaccines, Subunit/administration & dosage/genetics/immunology MH - Viral Vaccines/*administration & dosage/genetics/immunology OTO - NOTNLM OT - FMDV OT - HBHA OT - Multi-epitope vaccine OT - TLR4 agonist COIS- Declaration of Competing Interest All authors declare no competing interests. EDAT- 2020/03/22 06:00 MHDA- 2020/07/14 06:00 CRDT- 2020/03/22 06:00 PHST- 2019/10/07 00:00 [received] PHST- 2020/02/02 00:00 [revised] PHST- 2020/02/25 00:00 [accepted] PHST- 2020/03/22 06:00 [pubmed] PHST- 2020/07/14 06:00 [medline] PHST- 2020/03/22 06:00 [entrez] AID - S0161-5890(19)30692-3 [pii] AID - 10.1016/j.molimm.2020.02.018 [doi] PST - ppublish SO - Mol Immunol. 2020 May;121:118-126. doi: 10.1016/j.molimm.2020.02.018. Epub 2020 Mar 18.