Intranasal immunization with a replication-deficient adenoviral vector expressing the fusion glycoprotein of respiratory syncytial virus elicits protective immunity in BALB/c mice |
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Authors: | Yuanhui Fu Jinsheng He Xianxian Zheng Mei Zhang Yan Wang Qian Tang Min Wang Jianguo Qu Xin Wang |
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Institution: | a Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China b College of Life Sciences & Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044, China c Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032, China d Department of Pathology, Anhui Medical University, Hefei, Anhui, 230032, China |
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Abstract: | Human respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract worldwide. There is currently no clinically approved vaccine against RSV infection. Recently, it has been shown that a replication-deficient first generation adenoviral vector (FGAd), which encodes modified RSV attachment glycoprotein (G), elicits long-term protective immunity against RSV infection in mice. The major problem in developing such a vaccine is that G protein lacks MHC-I-restricted epitopes. However, RSV fusion glycoprotein (F) is a major cytotoxic T-lymphocyte epitope in humans and mice, therefore, an FGAd-encoding F (FGAd-F) was constructed and evaluated for its potential as an RSV vaccine in a murine model. Intranasal (i.n.) immunization with FGAd-F generated serum IgG, bronchoalveolar lavage secretory IgA, and RSV-specific CD8+ T-cell responses in BALB/c mice, with characteristic balanced or mixed Th1/Th2 CD4+ T-cell responses. Serum IgG was significantly elevated after boosting with i.n. FGAd-F. Upon challenge, i.n. immunization with FGAd-F displayed an effective protective role against RSV infection. These results demonstrate FGAd-F is able to induce effective protective immunity and is a promising vaccine regimen against RSV infection. |
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Keywords: | Human respiratory syncytial virus Replication-deficient adenoviral vector Protective immunity |
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