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 4

The schedule of the vaccine regimens and the humoral immune response induced in hamsters.

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The schedule of the vaccine regimens and the humoral immune response ind...
(A) The schedule of the vaccine regimens conducted in hamsters. After the hamsters received 2 or 3 doses of vaccine immunization, either NiV-M or NiV-B was injected into the hamsters. Subsequently, weight and survival were monitored daily until 21 days after the challenge. Five days after the virus challenge, 6 hamsters of each group were scarified for viral and pathological detection. (B) F-specific IgG induced by the vaccine regimens. All 3 vaccine regimens induced high levels of IgG antibodies, and the titers of IgG were elevated with increasing immunization times (n = 6). (C) The NAs in different vaccine regimen–immunized sera of hamsters by pseudovirus neutralization assay. Consistent with the level of IgG, the vaccine regimens induced high titers of NAs, which increased with increasing immunization time (n = 6). (D) The NAs in different vaccine regimen–immunized sera of hamsters detected by microneutralization assay of NiV-M and NiV-B. Most of the hamsters (except 1) immunized with the vaccine regimens developed high titers of NAs against NiV-M and NiV-B at the same time (n = 6). Data are presented as the group mean ± SEM. Statistical significance was determined by 1-way ANOVA with Tukey’s multiple-comparison test (D). Two-tailed, unpaired Student’s t tests were conducted to compare differences between 2 experimental groups (B and C). NS, not significant. ****P < 0.0001.