A Novel, Comprehensive A129 Mouse Model for Investigating Dengue Vaccines and Evaluating Pathogenesis
In search of a mouse model for use in evaluating dengue vaccines, we assessed A129 mice that lacked IFN-α/β receptors, rendering them susceptible to dengue virus (DENV) infection. To our knowledge, no reports have evaluated dengue vaccine efficiency using A129 mice. A129 mice were given a single int...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/12/1857 |
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| author | Mya Myat Ngwe Tun Khine Mya Nwe Jean Claude Balingit Yuki Takamatsu Shingo Inoue Basu Dev Pandey Takeshi Urano Michinori Kohara Kyoko Tsukiyama-Kohara Kouichi Morita |
| author_facet | Mya Myat Ngwe Tun Khine Mya Nwe Jean Claude Balingit Yuki Takamatsu Shingo Inoue Basu Dev Pandey Takeshi Urano Michinori Kohara Kyoko Tsukiyama-Kohara Kouichi Morita |
| author_sort | Mya Myat Ngwe Tun |
| collection | DOAJ |
| description | In search of a mouse model for use in evaluating dengue vaccines, we assessed A129 mice that lacked IFN-α/β receptors, rendering them susceptible to dengue virus (DENV) infection. To our knowledge, no reports have evaluated dengue vaccine efficiency using A129 mice. A129 mice were given a single intraperitoneal (IP) or subcutaneous (SC) injection of the vaccine, Dengvaxia. After 14 days of immunization via the IP or SC injection of Dengvaxia, the A129 mice exhibited notably elevated levels of anti-DENV immunoglobulin G and neutralizing antibodies (NAb) targeting all four DENV serotypes, with DENV-4 displaying the highest NAb levels. After challenge with DENV-2, Dengvaxia and mock-immunized mice survived, while only the mock group exhibited signs of morbidity. Viral genome levels in the serum and tissues (excluding the brain) were considerably lower in the immunized mice compared to those in the mock group. The SC administration of Dengvaxia resulted in lower viremia levels than IP administration did. Therefore, given that A129 mice manifest dengue-related morbidity, including viremia in the serum and other tissues, these mice represent a valuable model for investigating novel dengue vaccines and antiviral drugs and for exploring dengue pathogenesis. |
| first_indexed | 2024-03-08T20:18:20Z |
| format | Article |
| id | doaj.art-a9bbcb9d0a4641adb6397d08cd477cdc |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-08T20:18:20Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-a9bbcb9d0a4641adb6397d08cd477cdc2023-12-22T14:47:36ZengMDPI AGVaccines2076-393X2023-12-011112185710.3390/vaccines11121857A Novel, Comprehensive A129 Mouse Model for Investigating Dengue Vaccines and Evaluating PathogenesisMya Myat Ngwe Tun0Khine Mya Nwe1Jean Claude Balingit2Yuki Takamatsu3Shingo Inoue4Basu Dev Pandey5Takeshi Urano6Michinori Kohara7Kyoko Tsukiyama-Kohara8Kouichi Morita9Department of Tropical Viral Vaccine Development, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, JapanDepartment of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, JapanDepartment of Tropical Viral Vaccine Development, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, JapanDepartment of Tropical Viral Vaccine Development, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, JapanKenya Research Station, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, JapanDejima Infectious Diseases Research Alliance, Nagasaki University, Nagasaki 852-8523, JapanCenter for Vaccines and Therapeutic Antibodies for Emerging Infectious Diseases, Shimane University, Izumo 690-8504, JapanDepartment of Diseases and Infection, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-0057, JapanTransboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, JapanDepartment of Tropical Viral Vaccine Development, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, JapanIn search of a mouse model for use in evaluating dengue vaccines, we assessed A129 mice that lacked IFN-α/β receptors, rendering them susceptible to dengue virus (DENV) infection. To our knowledge, no reports have evaluated dengue vaccine efficiency using A129 mice. A129 mice were given a single intraperitoneal (IP) or subcutaneous (SC) injection of the vaccine, Dengvaxia. After 14 days of immunization via the IP or SC injection of Dengvaxia, the A129 mice exhibited notably elevated levels of anti-DENV immunoglobulin G and neutralizing antibodies (NAb) targeting all four DENV serotypes, with DENV-4 displaying the highest NAb levels. After challenge with DENV-2, Dengvaxia and mock-immunized mice survived, while only the mock group exhibited signs of morbidity. Viral genome levels in the serum and tissues (excluding the brain) were considerably lower in the immunized mice compared to those in the mock group. The SC administration of Dengvaxia resulted in lower viremia levels than IP administration did. Therefore, given that A129 mice manifest dengue-related morbidity, including viremia in the serum and other tissues, these mice represent a valuable model for investigating novel dengue vaccines and antiviral drugs and for exploring dengue pathogenesis.https://www.mdpi.com/2076-393X/11/12/1857A129 mouseDengvaxia vaccinedengue virusneutralization antibodyviral loads |
| spellingShingle | Mya Myat Ngwe Tun Khine Mya Nwe Jean Claude Balingit Yuki Takamatsu Shingo Inoue Basu Dev Pandey Takeshi Urano Michinori Kohara Kyoko Tsukiyama-Kohara Kouichi Morita A Novel, Comprehensive A129 Mouse Model for Investigating Dengue Vaccines and Evaluating Pathogenesis Vaccines A129 mouse Dengvaxia vaccine dengue virus neutralization antibody viral loads |
| title | A Novel, Comprehensive A129 Mouse Model for Investigating Dengue Vaccines and Evaluating Pathogenesis |
| title_full | A Novel, Comprehensive A129 Mouse Model for Investigating Dengue Vaccines and Evaluating Pathogenesis |
| title_fullStr | A Novel, Comprehensive A129 Mouse Model for Investigating Dengue Vaccines and Evaluating Pathogenesis |
| title_full_unstemmed | A Novel, Comprehensive A129 Mouse Model for Investigating Dengue Vaccines and Evaluating Pathogenesis |
| title_short | A Novel, Comprehensive A129 Mouse Model for Investigating Dengue Vaccines and Evaluating Pathogenesis |
| title_sort | novel comprehensive a129 mouse model for investigating dengue vaccines and evaluating pathogenesis |
| topic | A129 mouse Dengvaxia vaccine dengue virus neutralization antibody viral loads |
| url | https://www.mdpi.com/2076-393X/11/12/1857 |
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