期刊
JOURNAL OF INFECTIOUS DISEASES
卷 218, 期 3, 页码 365-377出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiy187
关键词
adenovirus; envelope; premembrane; vaccine; Zika
资金
- Hong Kong Hainan Commercial Association South China Microbiology Research Fund
- Chan Yin Chuen Memorial Charitable Foundation
- Hui Hoy and Chow Sin Lan Charity Fund Limited
- Zika Special Project of the MOST (Ministry of Science and Technology) Reform and Development Project of China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the Ministry of Education of China
Background. Zika virus (ZIKV) infection may be associated with severe complications and disseminated via both vector-borne and nonvector-borne routes. Adenovirus-vectored vaccines represent a favorable controlling measure for the ZIKV epidemic because they have been shown to be safe, immunogenic, and rapidly generable for other emerging viral infections. Evaluations of 2 previously reported adenovirus-vectored ZIKV vaccines were performed using nonlethal animal models and/or nonepidemic ZIKV strain. Methods. We constructed 2 novel human adenovirus 5 (Ad5)-vectored vaccines containing the ZIKV premembrane-envelope (Ad5-Sig-prM-Env) and envelope (Ad5-Env) proteins, respectively, and evaluated them in multiple nonlethal and lethal animal models using epidemic ZIKV strains. Results. Both vaccines elicited robust humoral and cellular immune responses in immunocompetent BALB/c mice. Dexamethasone-immunosuppressed mice vaccinated with either vaccine demonstrated robust and durable antibody responses and significantly lower blood and tissue viral loads than controls (P < .05). Similar findings were also observed in interferon-alpha/beta receptor-deficient A129 mice. In both of these immunocompromised animal models, Ad5-Sig-prM-Env-vaccinated mice had significantly (P < .05) higher titers of anti-ZIKV-specific neutralizing antibody titers and lower (undetectable) viral loads than Ad5-Env-vaccinated mice. The close correlation between the neutralizing antibody titer and viral load helped to explain the better protective effect of Ad5-Sig-prM-Env than Ad5-Env. Anamnestic response was absent in Ad5-Sig-prM-Env-vaccinated A129 mice. Conclusions. Ad5-Sig-prM-Env provided sterilizing protection against ZIKV infection in mice.
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