Evaluation of Vertebrate-Specific Replication-Defective Zika Virus, a Novel Single-Cycle Arbovirus Vaccine, in a Mouse Model
| Autor: | Weidong Yan, Yanfei Zhou, Xinbin Gu, Shengbo Cao, Tzyy Choou Wu, Shengfeng Wan, Xugang Wang, Xiaowu Pang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
safety viruses Immunology cellular and humoral immune response lcsh:Medicine vertebrate-specific replication-defective Zika virus Arbovirus Article Zika virus 03 medical and health sciences 0302 clinical medicine Immune system Immunity Drug Discovery medicine Pharmacology (medical) 030212 general & internal medicine single-cycle arbovirus vaccine Pharmacology artificial insect-specific virus biology Immunogenicity lcsh:R biochemical phenomena metabolism and nutrition biology.organism_classification medicine.disease Virology immunity Flavivirus Titer 030104 developmental biology Infectious Diseases Immunization |
| Zdroj: | Vaccines, Vol 9, Iss 338, p 338 (2021) Vaccines Volume 9 Issue 4 |
| Popis: | The flavivirus Zika (ZIKV) has emerged as a global threat, making the development of a ZIKV vaccine a priority. While live-attenuated vaccines are known to induce long-term immunity but reduced safety, inactivated vaccines exhibit a weaker immune response as a trade-off for increased safety margins. To overcome the trade-off between immunogenicity and safety, the concept of a third-generation flavivirus vaccine based on single-cycle flaviviruses has been developed. These third-generation flavivirus vaccines have demonstrated extreme potency with a high level of safety in animal models. However, the production of these single-cycle, encapsidation-defective flaviviruses requires a complicated virion packaging system. Here, we investigated a new single-cycle flavivirus vaccine, a vertebrate-specific replication-defective ZIKV (VSRD-ZIKV), in a mouse model. VSRD-ZIKV replicates to high titers in insect cells but can only initiate a single-round infection in vertebrate cells. During a single round of infection, VSRD-ZIKV can express all the authentic viral antigens in vertebrate hosts. VSRD-ZIKV immunization elicited a robust cellular and humoral immune response that protected against a lethal ZIKV challenge in AG129 mice. Additionally, VSRD-ZIKV-immunized pregnant mice were protected against vertically transferring a lethal ZIKV infection to their offspring. Immunized male mice were protected and prevented viral accumulation in the testes after being challenged with lethal ZIKV. Overall, our results indicate that VSRD-ZIKV induces a potent protective immunity against ZIKV in a mouse model and represents a promising approach to develop novel single-cycle arbovirus vaccines. |
| Databáze: | OpenAIRE |
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