Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice

Rift Valley fever virus (RVFV), which causes Rift Valley fever (RVF), is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. RVF is a World Health Organization (WHO) priority disease and, together with rabies, is a major health burden in Africa. He...

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Main Authors: Shengnan Zhang, Meng Hao, Na Feng, Hongli Jin, Feihu Yan, Hang Chi, Hualei Wang, Qiuxue Han, Jianzhong Wang, Gary Wong, Bo Liu, Jun Wu, Yuhai Bi, Tiecheng Wang, Weiyang Sun, Yuwei Gao, Songtao Yang, Yongkun Zhao, Xianzhu Xia
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/11/10/919
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language English
format Article
sources DOAJ
author Shengnan Zhang
Meng Hao
Na Feng
Hongli Jin
Feihu Yan
Hang Chi
Hualei Wang
Qiuxue Han
Jianzhong Wang
Gary Wong
Bo Liu
Jun Wu
Yuhai Bi
Tiecheng Wang
Weiyang Sun
Yuwei Gao
Songtao Yang
Yongkun Zhao
Xianzhu Xia
spellingShingle Shengnan Zhang
Meng Hao
Na Feng
Hongli Jin
Feihu Yan
Hang Chi
Hualei Wang
Qiuxue Han
Jianzhong Wang
Gary Wong
Bo Liu
Jun Wu
Yuhai Bi
Tiecheng Wang
Weiyang Sun
Yuwei Gao
Songtao Yang
Yongkun Zhao
Xianzhu Xia
Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice
Viruses
rift valley fever virus
rabies virus
inactivated vaccine
rvfv-specific igg antibodies
adjuvant
author_facet Shengnan Zhang
Meng Hao
Na Feng
Hongli Jin
Feihu Yan
Hang Chi
Hualei Wang
Qiuxue Han
Jianzhong Wang
Gary Wong
Bo Liu
Jun Wu
Yuhai Bi
Tiecheng Wang
Weiyang Sun
Yuwei Gao
Songtao Yang
Yongkun Zhao
Xianzhu Xia
author_sort Shengnan Zhang
title Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice
title_short Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice
title_full Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice
title_fullStr Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice
title_full_unstemmed Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice
title_sort genetically modified rabies virus vector-based rift valley fever virus vaccine is safe and induces efficacious immune responses in mice
publisher MDPI AG
series Viruses
issn 1999-4915
publishDate 2019-10-01
description Rift Valley fever virus (RVFV), which causes Rift Valley fever (RVF), is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. RVF is a World Health Organization (WHO) priority disease and, together with rabies, is a major health burden in Africa. Here, we present the development and characterization of an inactivated recombinant RVFV and rabies virus (RABV) vaccine candidate (rSRV9-eGn). Immunization with rSRV9-eGn stimulated the production of RVFV-specific IgG antibodies and induced humoral and cellular immunity in mice but did not induce the production of neutralizing antibodies. IgG1 and IgG2a were the main isotypes observed by IgG subtype detection, and IgG3 antibodies were not detected. The ratios of IgG1/IgG2a &gt; 1 indicated a Type 2 humoral immune response. An effective vaccine is intended to establish a long-lived population of memory T cells, and mice generated memory cells among the proliferating T cell population after immunization with rSRV9-eGn, with effector memory T cells (T<sub>EM</sub>) as the major population. Due to the lack of prophylactic treatment experiments, it is impossible to predict whether this vaccine can protect animals from RVFV infection with only high titres of anti-RVFV IgG antibodies and no neutralizing antibodies induced, and thus, protection confirmation needs further verification. However, this RVFV vaccine designed with RABV as the vector provides ideas for the development of vaccines that prevent RVFV and RABV infections.
topic rift valley fever virus
rabies virus
inactivated vaccine
rvfv-specific igg antibodies
adjuvant
url https://www.mdpi.com/1999-4915/11/10/919
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spelling doaj-dd5ae07893b0449784556f747c56a9082020-11-25T00:48:19ZengMDPI AGViruses1999-49152019-10-01111091910.3390/v11100919v11100919Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in MiceShengnan Zhang0Meng Hao1Na Feng2Hongli Jin3Feihu Yan4Hang Chi5Hualei Wang6Qiuxue Han7Jianzhong Wang8Gary Wong9Bo Liu10Jun Wu11Yuhai Bi12Tiecheng Wang13Weiyang Sun14Yuwei Gao15Songtao Yang16Yongkun Zhao17Xianzhu Xia18College of Wildlife and Protected Areas, Northeast Forestry University, Harbin 150040, ChinaComparative Medicine Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, ChinaAnimal Science and Technology College, Jilin Agricultural University, Changchun 130118, ChinaInstitute Pasteur of Shanghai, Chinese Academy of Science, Shanghai 20031, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, ChinaRift Valley fever virus (RVFV), which causes Rift Valley fever (RVF), is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. RVF is a World Health Organization (WHO) priority disease and, together with rabies, is a major health burden in Africa. Here, we present the development and characterization of an inactivated recombinant RVFV and rabies virus (RABV) vaccine candidate (rSRV9-eGn). Immunization with rSRV9-eGn stimulated the production of RVFV-specific IgG antibodies and induced humoral and cellular immunity in mice but did not induce the production of neutralizing antibodies. IgG1 and IgG2a were the main isotypes observed by IgG subtype detection, and IgG3 antibodies were not detected. The ratios of IgG1/IgG2a &gt; 1 indicated a Type 2 humoral immune response. An effective vaccine is intended to establish a long-lived population of memory T cells, and mice generated memory cells among the proliferating T cell population after immunization with rSRV9-eGn, with effector memory T cells (T<sub>EM</sub>) as the major population. Due to the lack of prophylactic treatment experiments, it is impossible to predict whether this vaccine can protect animals from RVFV infection with only high titres of anti-RVFV IgG antibodies and no neutralizing antibodies induced, and thus, protection confirmation needs further verification. However, this RVFV vaccine designed with RABV as the vector provides ideas for the development of vaccines that prevent RVFV and RABV infections.https://www.mdpi.com/1999-4915/11/10/919rift valley fever virusrabies virusinactivated vaccinervfv-specific igg antibodiesadjuvant