An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens.

The global spread of Zika virus (ZIKV), which caused a pandemic associated with Congenital Zika Syndrome and neuropathology in newborns and adults, prompted the pursuit of a safe and effective vaccine. Here, three kinds of recombinant rabies virus (RABV) encoding the prM-E protein of ZIKV were const...

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Autores principales:	Hongli Jin, Cuicui Jiao, Zengguo Cao, Pei Huang, Hang Chi, Yujie Bai, Di Liu, Jianzhong Wang, Na Feng, Nan Li, Yongkun Zhao, Tiecheng Wang, Yuwei Gao, Songtao Yang, Xianzhu Xia, Hualei Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/ba885491555e46738a09e5d5f956d0ae
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spelling	oai:doaj.org-article:ba885491555e46738a09e5d5f956d0ae2021-11-25T06:33:09ZAn inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens.1935-27271935-273510.1371/journal.pntd.0009484https://doaj.org/article/ba885491555e46738a09e5d5f956d0ae2021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009484https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735The global spread of Zika virus (ZIKV), which caused a pandemic associated with Congenital Zika Syndrome and neuropathology in newborns and adults, prompted the pursuit of a safe and effective vaccine. Here, three kinds of recombinant rabies virus (RABV) encoding the prM-E protein of ZIKV were constructed: ZI-D (prM-E), ZI-E (transmembrane domain (TM) of prM-E replaced with RABV G) and ZI-F (signal peptide and TM domain of prM-E replaced with the region of RABV G). When the TM of prM-E was replaced with the region of RABV G (termed ZI-E), it promoted ZIKV E protein localization on the cell membrane and assembly on recombinant viruses. In addition, the change in the signal peptide with RABV G (termed ZI-F) was not conducive to foreign protein expression. The immunogenicity of recombinant viruses mixed with a complex adjuvant of ISA 201 VG and poly(I:C) was tested in BALB/c mice. After immunization with ZI-E, the anti-ZIKV IgG antibody lasted for at least 10 weeks. The titers of neutralizing antibodies (NAbs) against ZIKV and RABV at week 6 were all greater than the protective titers. Moreover, ZI-E stimulated the proliferation of splenic lymphocytes and promoted the secretion of cytokines. It also promoted the production of central memory T cells (TCMs) among CD4+/CD8+ T cells and stimulated B cell activation and maturation. These results indicate that ZI-E could induce ZIKV-specific humoral and cellular immune responses, which have the potential to be developed into a promising vaccine for protection against both ZIKV and RABV infections.Hongli JinCuicui JiaoZengguo CaoPei HuangHang ChiYujie BaiDi LiuJianzhong WangNa FengNan LiYongkun ZhaoTiecheng WangYuwei GaoSongtao YangXianzhu XiaHualei WangPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 6, p e0009484 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Hongli Jin Cuicui Jiao Zengguo Cao Pei Huang Hang Chi Yujie Bai Di Liu Jianzhong Wang Na Feng Nan Li Yongkun Zhao Tiecheng Wang Yuwei Gao Songtao Yang Xianzhu Xia Hualei Wang An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens.
description	The global spread of Zika virus (ZIKV), which caused a pandemic associated with Congenital Zika Syndrome and neuropathology in newborns and adults, prompted the pursuit of a safe and effective vaccine. Here, three kinds of recombinant rabies virus (RABV) encoding the prM-E protein of ZIKV were constructed: ZI-D (prM-E), ZI-E (transmembrane domain (TM) of prM-E replaced with RABV G) and ZI-F (signal peptide and TM domain of prM-E replaced with the region of RABV G). When the TM of prM-E was replaced with the region of RABV G (termed ZI-E), it promoted ZIKV E protein localization on the cell membrane and assembly on recombinant viruses. In addition, the change in the signal peptide with RABV G (termed ZI-F) was not conducive to foreign protein expression. The immunogenicity of recombinant viruses mixed with a complex adjuvant of ISA 201 VG and poly(I:C) was tested in BALB/c mice. After immunization with ZI-E, the anti-ZIKV IgG antibody lasted for at least 10 weeks. The titers of neutralizing antibodies (NAbs) against ZIKV and RABV at week 6 were all greater than the protective titers. Moreover, ZI-E stimulated the proliferation of splenic lymphocytes and promoted the secretion of cytokines. It also promoted the production of central memory T cells (TCMs) among CD4+/CD8+ T cells and stimulated B cell activation and maturation. These results indicate that ZI-E could induce ZIKV-specific humoral and cellular immune responses, which have the potential to be developed into a promising vaccine for protection against both ZIKV and RABV infections.
format	article
author	Hongli Jin Cuicui Jiao Zengguo Cao Pei Huang Hang Chi Yujie Bai Di Liu Jianzhong Wang Na Feng Nan Li Yongkun Zhao Tiecheng Wang Yuwei Gao Songtao Yang Xianzhu Xia Hualei Wang
author_facet	Hongli Jin Cuicui Jiao Zengguo Cao Pei Huang Hang Chi Yujie Bai Di Liu Jianzhong Wang Na Feng Nan Li Yongkun Zhao Tiecheng Wang Yuwei Gao Songtao Yang Xianzhu Xia Hualei Wang
author_sort	Hongli Jin
title	An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens.
title_short	An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens.
title_full	An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens.
title_fullStr	An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens.
title_full_unstemmed	An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens.
title_sort	inactivated recombinant rabies virus displaying the zika virus prm-e induces protective immunity against both pathogens.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/ba885491555e46738a09e5d5f956d0ae
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An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens.

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