title: Construction and preliminary investigation of a novel dengue serotype 4 chimeric virus using Japanese encephalitis vaccine strain SA14-14-2 as the backbone.
abstract: For the purpose of developing a novel dengue vaccine candidate, recombinant plasmids were constructed which contained the full length cDNA clone of Japanese encephalitis (JE) vaccine strain SA14-14-2 with its premembrane (PreM) and envelope (E) genes replaced by the counterparts of dengue virus type 4 (DENV4). By transfecting the in vitro transcription products of the recombinant plasmids into BHK-21 cells, a chimeric virus JEV/DENV4 was successfully recovered. The chimeric virus was identified by complete genome sequencing, Western blot and immunofluorescent staining. Growth characteristics revealed it was well adapted to primary hamster kidney (PHK) cells. Its genetic stability was investigated and only one unintentional mutation in 5'-untranslated region (5'-UTR) was found after 20 passages in PHK cells. Neurotropism, neurovirulence and immunogenicity of the chimeric virus were tested in mice. Besides, the influence of JE vaccine pre-immunization on the neutralizing antibody level induced by the chimeric virus was illuminated. To our knowledge, this is the first chimeric virus incorporating the JE vaccine stain SA14-14-2 and DENV4. It is probably a potential candidate to compose a tetravalent dengue chimeric vaccine.
authors.affiliation: Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China.
authors.forename: Zhushi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China.
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China.
authors.forename: Xianwu
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 100050, China. Electronic address: liyuhua@hotmail.com.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D006224:Cricetinae; D003715:Dengue / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003716:Dengue Virus / Q000145:classification / Q000235:genetics* / Q000276:immunology; D004664:Encephalitis Virus, Japanese / Q000235:genetics* / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics* / Q000276:immunology; D006801:Humans; D022321:Japanese Encephalitis Vaccines / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D053059:Dengue Vaccines; D022321:Japanese Encephalitis Vaccines; D014759:Viral Envelope Proteins
keywords: Chimeric virus; Dengue virus (DENV); Immunogenicity; Japanese encephalitis virus (JEV); Neurotropism; Neurovirulence