Vaccines based on the fusion protein consensus sequence protect Syrian hamsters from Nipah virus infection
Mingqing Lu, Yanfeng Yao, Hang Liu, Xuekai Zhang, Xuejie Li, Yuanhua Liu, Yun Peng, Tong Chen, Yun Sun, Ge Gao, Miaoyu Chen, Jiaxuan Zhao, XiaoYu Zhang, Chunhong Yin, Weiwei Guo, Peipei Yang, Xue Hu, Juhong Rao, Entao Li, Gary Wong, Zhiming Yuan, Sandra Chiu, Chao Shan, Jiaming Lan
Mingqing Lu, Yanfeng Yao, Hang Liu, Xuekai Zhang, Xuejie Li, Yuanhua Liu, Yun Peng, Tong Chen, Yun Sun, Ge Gao, Miaoyu Chen, Jiaxuan Zhao, XiaoYu Zhang, Chunhong Yin, Weiwei Guo, Peipei Yang, Xue Hu, Juhong Rao, Entao Li, Gary Wong, Zhiming Yuan, Sandra Chiu, Chao Shan, Jiaming Lan
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Research Article Vaccines Virology

Vaccines based on the fusion protein consensus sequence protect Syrian hamsters from Nipah virus infection

Abstract

Nipah virus (NiV), a bat-borne paramyxovirus, results in neurological and respiratory diseases with high mortality in humans and animals. Developing vaccines is crucial for fighting these diseases. Previously, only a few studies focused on the fusion (F) protein alone as the immunogen. Numerous NiV strains have been identified, including 2 representative strains from Malaysia (NiV-M) and Bangladesh (NiV-B), which differ significantly from each other. In this study, an F protein sequence with the potential to prevent different NiV strain infections was designed by bioinformatics analysis after an in-depth study of NiV sequences in GenBank. Then, a chimpanzee adenoviral vector vaccine and a DNA vaccine were developed. High levels of immune responses were detected after AdC68-F, pVAX1-F, and a prime-boost strategy (pVAX1-F/AdC68-F) in mice. After high titers of humoral responses were induced, the hamsters were challenged by the lethal NiV-M and NiV-B strains separately. The vaccinated hamsters did not show any clinical signs and survived 21 days after infection with either strain of NiV, and no virus was detected in different tissues. These results indicate that the vaccines provided complete protection against representative strains of NiV infection and have the potential to be developed as a broad-spectrum vaccine for human use.

Authors

Mingqing Lu, Yanfeng Yao, Hang Liu, Xuekai Zhang, Xuejie Li, Yuanhua Liu, Yun Peng, Tong Chen, Yun Sun, Ge Gao, Miaoyu Chen, Jiaxuan Zhao, XiaoYu Zhang, Chunhong Yin, Weiwei Guo, Peipei Yang, Xue Hu, Juhong Rao, Entao Li, Gary Wong, Zhiming Yuan, Sandra Chiu, Chao Shan, Jiaming Lan

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Figure 6

Viral nucleic acid load and viral titers in different tissues of hamsters after challenge with NiV.

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Viral nucleic acid load and viral titers in different tissues of hamster...
Five days after NiV-M or NiV-B infection, 6 hamsters were randomly selected and euthanized to collect the lung, brain, and spleen tissues. Real-time PCR and virus titration experiments showed that hamsters of empty vector groups (n = 6) infected with NiV-M had a high viral load in the lung, brain, and spleen tissues, while vaccinated hamsters had no viral nucleic acid (A) or infectious viral particles (B). Similarly, after NiV-B infection, most animals (except for 2 of AdC68 in the brain, 1 of pVAX1 in the brain, 2 of pVAX1/AdC68 in the brain, 1 of AdC68 in the spleen, and 1 of pVAX1 in the spleen) in the empty vector control groups showed high viral load (C) and infectious viral particles (D) in the lung, brain, and spleen tissues, while the vaccine regimens protected the hamsters against the virus without any viral nucleic acid or infectious viral particles in these tissues. Data are shown as the mean ± SEM. Two-tailed, unpaired Student’s t tests were conducted to compare differences between 2 experimental groups. ****P < 0.0001.