A Bivalent Human Adenovirus Type 5 Vaccine Expressing the Rabies Virus Glycoprotein and Canine Distemper Virus Hemagglutinin Protein Confers Protective Immunity in Mice and Foxes
The development of a safe and efficient multivalent vaccine has great prospects for application. Both rabies virus (RABV) and canine distemper virus (CDV) are highly infectious antigens, causing lethal diseases in domestic dogs and other carnivores worldwide. In this study, a replication-deficient h...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-06-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2020.01070/full |
| _version_ | 1829102436435886080 |
|---|---|
| author | Lina Yan Zhongxin Zhao Xianghong Xue Wenwen Zheng Tong Xu Lele Liu Li Tian Xianwei Wang Hongbin He Xuexing Zheng |
| author_facet | Lina Yan Zhongxin Zhao Xianghong Xue Wenwen Zheng Tong Xu Lele Liu Li Tian Xianwei Wang Hongbin He Xuexing Zheng |
| author_sort | Lina Yan |
| collection | DOAJ |
| description | The development of a safe and efficient multivalent vaccine has great prospects for application. Both rabies virus (RABV) and canine distemper virus (CDV) are highly infectious antigens, causing lethal diseases in domestic dogs and other carnivores worldwide. In this study, a replication-deficient human adenovirus 5 (Ad5)-vectored vaccine, rAd5-G-H, expressing RABV glycoprotein (G) and CDV hemagglutinin (H) protein was constructed. The RABV G and CDV H protein of rAd5-G-H were expressed and confirmed in infected HEK-293 cells by indirect immunofluorescence assay. The rAd5-G-H retained a homogeneous icosahedral morphology similar to rAd5-GFP under an electron microscope. A single dose of 108 GFU of rAd5-G-H administered to mice by intramuscular injection elicited rapid and robust neutralizing antibodies against RABV and CDV. Flow cytometry assays indicated that the dendritic cells and B cells in inguinal lymph nodes were significantly recruited in rAd5-G-H-immunized mice in comparison with the mock and rAd5-GFP groups. rAd5-G-H also activated the Th1- and Th2-mediated cell immune responses against RABV and CDV in mice, which contributed to 100% survival of a lethal-dose RABV challenge without any clinical signs. In foxes, a single dose of 109 GFU of rAd5-G-H could elicit high levels of neutralizing antibodies against both RABV and CDV in comparison with the mock and rAd5-GFP groups. All foxes in the rAd5-GFP and mock groups died, while the foxes inoculated with rAd5-G-H all survived and showed no clinical signs of disease after being challenged with a lethal wild-type CDV strain. These results suggested that rAd5-G-H has great potential as a bivalent vaccine against rabies and canine distemper in highly susceptible dogs and wildlife animals. |
| first_indexed | 2024-12-10T23:00:16Z |
| format | Article |
| id | doaj.art-e7419d0787fe4ddf9696de922a2ba183 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-10T23:00:16Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-e7419d0787fe4ddf9696de922a2ba1832022-12-22T01:30:09ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-06-011110.3389/fmicb.2020.01070522909A Bivalent Human Adenovirus Type 5 Vaccine Expressing the Rabies Virus Glycoprotein and Canine Distemper Virus Hemagglutinin Protein Confers Protective Immunity in Mice and FoxesLina Yan0Zhongxin Zhao1Xianghong Xue2Wenwen Zheng3Tong Xu4Lele Liu5Li Tian6Xianwei Wang7Hongbin He8Xuexing Zheng9Department of Virology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Virology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDivisions of Infectious Diseases of Special Animal, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, ChinaDepartment of Virology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Virology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Virology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Virology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Life Sciences, Shandong University, Qingdao, ChinaCollege of Life Sciences, Shandong Normal University, Jinan, ChinaDepartment of Virology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, ChinaThe development of a safe and efficient multivalent vaccine has great prospects for application. Both rabies virus (RABV) and canine distemper virus (CDV) are highly infectious antigens, causing lethal diseases in domestic dogs and other carnivores worldwide. In this study, a replication-deficient human adenovirus 5 (Ad5)-vectored vaccine, rAd5-G-H, expressing RABV glycoprotein (G) and CDV hemagglutinin (H) protein was constructed. The RABV G and CDV H protein of rAd5-G-H were expressed and confirmed in infected HEK-293 cells by indirect immunofluorescence assay. The rAd5-G-H retained a homogeneous icosahedral morphology similar to rAd5-GFP under an electron microscope. A single dose of 108 GFU of rAd5-G-H administered to mice by intramuscular injection elicited rapid and robust neutralizing antibodies against RABV and CDV. Flow cytometry assays indicated that the dendritic cells and B cells in inguinal lymph nodes were significantly recruited in rAd5-G-H-immunized mice in comparison with the mock and rAd5-GFP groups. rAd5-G-H also activated the Th1- and Th2-mediated cell immune responses against RABV and CDV in mice, which contributed to 100% survival of a lethal-dose RABV challenge without any clinical signs. In foxes, a single dose of 109 GFU of rAd5-G-H could elicit high levels of neutralizing antibodies against both RABV and CDV in comparison with the mock and rAd5-GFP groups. All foxes in the rAd5-GFP and mock groups died, while the foxes inoculated with rAd5-G-H all survived and showed no clinical signs of disease after being challenged with a lethal wild-type CDV strain. These results suggested that rAd5-G-H has great potential as a bivalent vaccine against rabies and canine distemper in highly susceptible dogs and wildlife animals.https://www.frontiersin.org/article/10.3389/fmicb.2020.01070/fullhuman adenovirus 5rabies viruscanine distemper virusglycoproteinhemagglutininbivalent vaccine |
| spellingShingle | Lina Yan Zhongxin Zhao Xianghong Xue Wenwen Zheng Tong Xu Lele Liu Li Tian Xianwei Wang Hongbin He Xuexing Zheng A Bivalent Human Adenovirus Type 5 Vaccine Expressing the Rabies Virus Glycoprotein and Canine Distemper Virus Hemagglutinin Protein Confers Protective Immunity in Mice and Foxes Frontiers in Microbiology human adenovirus 5 rabies virus canine distemper virus glycoprotein hemagglutinin bivalent vaccine |
| title | A Bivalent Human Adenovirus Type 5 Vaccine Expressing the Rabies Virus Glycoprotein and Canine Distemper Virus Hemagglutinin Protein Confers Protective Immunity in Mice and Foxes |
| title_full | A Bivalent Human Adenovirus Type 5 Vaccine Expressing the Rabies Virus Glycoprotein and Canine Distemper Virus Hemagglutinin Protein Confers Protective Immunity in Mice and Foxes |
| title_fullStr | A Bivalent Human Adenovirus Type 5 Vaccine Expressing the Rabies Virus Glycoprotein and Canine Distemper Virus Hemagglutinin Protein Confers Protective Immunity in Mice and Foxes |
| title_full_unstemmed | A Bivalent Human Adenovirus Type 5 Vaccine Expressing the Rabies Virus Glycoprotein and Canine Distemper Virus Hemagglutinin Protein Confers Protective Immunity in Mice and Foxes |
| title_short | A Bivalent Human Adenovirus Type 5 Vaccine Expressing the Rabies Virus Glycoprotein and Canine Distemper Virus Hemagglutinin Protein Confers Protective Immunity in Mice and Foxes |
| title_sort | bivalent human adenovirus type 5 vaccine expressing the rabies virus glycoprotein and canine distemper virus hemagglutinin protein confers protective immunity in mice and foxes |
| topic | human adenovirus 5 rabies virus canine distemper virus glycoprotein hemagglutinin bivalent vaccine |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2020.01070/full |
| work_keys_str_mv | AT linayan abivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT zhongxinzhao abivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT xianghongxue abivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT wenwenzheng abivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT tongxu abivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT leleliu abivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT litian abivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT xianweiwang abivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT hongbinhe abivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT xuexingzheng abivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT linayan bivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT zhongxinzhao bivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT xianghongxue bivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT wenwenzheng bivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT tongxu bivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT leleliu bivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT litian bivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT xianweiwang bivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT hongbinhe bivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes AT xuexingzheng bivalenthumanadenovirustype5vaccineexpressingtherabiesvirusglycoproteinandcaninedistempervirushemagglutininproteinconfersprotectiveimmunityinmiceandfoxes |