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
View: Text | PDF
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

×

Figure 3

The immune schedules and immune responses to the vaccine regimens induced in mice.

Options: View larger image (or click on image) Download as PowerPoint
The immune schedules and immune responses to the vaccine regimens induce...
(A) The immune schedules of the mice. The mice were immunized once (i), twice (ii), or 3 times (iii). The sera and spleen tissues were harvested at different times for humoral and cellular immune response detection. (B) F-specific cellular immune responses were detected by ELISpot. Ten days after each immunization, the splenocytes of 6 mice in each vaccine group were collected (control group n = 3), and the number of T lymphocytes that could secrete IFN-γ is shown on the y axis under the stimulation with F peptides. SFC, spot-forming cells. P values are indicated in the graph. (C) The F-specific IgG antibodies and NAs induced by the pVAX1-F vaccine regimens were detected by ELISA and pseudovirus neutralization assay. Sera were collected at different times (2, 5, 8, 10, and 16 weeks) after the first immunization from each group. The dashed line represents the lower limit of detection (20 × dilution) (control group n = 3, vaccination group n = 6). (D) The F-specific IgG antibodies and NAs detected by ELISA and the pseudovirus neutralization assay in AdC68-F and pVAX1-F/AdC68-F vaccine regimens. The sera were collected at different times (2, 4, 6, 10, 14, 18, 22, 28, 32, 36, and 40 weeks) after the last immunization (control group n = 3, vaccination group n = 6). The F-specific IgG antibodies (IgG, upper) and neutralization antibodies (NAs, lower) are shown. The dashed line represents the lower limit of detection (25 × dilution). Data are shown as the mean ± SEM. Statistical significance was determined by 1-way ANOVA with Tukey’s multiple-comparison test. NS, not significant.