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 8

H&E and IHC staining of lungs and spleens after challenge with NiV-M.

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H&E and IHC staining of lungs and spleens after challenge with NiV-M...
(A) The lung of control hamsters exhibited hemorrhage within the alveolar walls and alveoli, extensive infiltration of lymphocytes and mononuclear macrophages, and significant inflammatory reactions in blood vessels and pleura, with edema fluid and fibrinous exudates in the alveoli. The lungs of vaccine regimen hamsters showed no significant histopathological abnormalities. (B) Lymphocytes in the spleens of control hamsters showed single-cell necrosis or focal necrosis, and there was a decrease in white pulp lymphocytes. However, only a few hamsters in the vaccine group showed a reduction in white pulp lymphocytes. (C) A large amount of NiV antigen was present in the lungs of nonimmunized control hamsters, while little or no NiV antigen was detected in the lungs of vaccinated hamsters. (D) A large amount of NiV antigen was present in the spleens of nonimmunized control hamsters, while no NiV antigen was detected in the spleens of vaccinated hamsters. Symbols corresponding to the distinct pathological lesions and signs are indicated on the right. Scale bars: 50 μm.