Construction and immunogenicity of an mRNA vaccine against chikungunya virus

被引:2
|
作者
Liu, Jingjing [1 ,2 ,3 ]
Lu, Xishan [4 ]
Li, Xingxing [3 ]
Huang, Weijin [5 ]
Fang, Enyue [3 ]
Li, Wenjuan [3 ]
Liu, Xiaohui [3 ]
Liu, Minglei [3 ]
Li, Jia [3 ]
Li, Ming [3 ]
Zhang, Zelun [3 ]
Song, Haifeng [4 ]
Ying, Bo [4 ]
Li, Yuhua [1 ,2 ,3 ]
机构
[1] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu, Peoples R China
[2] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu, Peoples R China
[3] Natl Inst Food & Drug Control, Div Arboviral Vaccines, Beijing, Peoples R China
[4] Suzhou Abogen Biosci Co Ltd, Dept Preclin Vaccine Res, Suzhou, Peoples R China
[5] Natl Inst Food & Drug Control, Div HIV AIDS & Sex Transmitted Virus Vaccines, Beijing, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷
关键词
chikungunya virus; mRNA vaccine; immunogenicity; sequential immunization; prime-boost; HEALTHY-ADULTS; FLOW-CYTOMETRY; TRANSLATION; INFECTION; RESPONSES; IMMUNITY; ELISPOT; PHASE-1; SAFETY;
D O I
10.3389/fimmu.2023.1129118
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Chikungunya fever (CHIKF) has spread to more than 100 countries worldwide, with frequent outbreaks in Europe and the Americas in recent years. Despite the relatively low lethality of infection, patients can suffer from long-term sequelae. Until now, no available vaccines have been approved for use; however, increasing attention is being paid to the development of vaccines against chikungunya virus (CHIKV), and the World Health Organization has included vaccine development in the initial blueprint deliverables. Here, we developed an mRNA vaccine using the nucleotide sequence encoding structural proteins of CHIKV. And immunogenicity was evaluated by neutralization assay, Enzyme-linked immunospot assay and Intracellular cytokine staining. The results showed that the encoded proteins elicited high levels of neutralizing antibody titers and T cell-mediated cellular immune responses in mice. Moreover, compared with the wild-type vaccine, the codon-optimized vaccine elicited robust CD8(+) T-cell responses and mild neutralizing antibody titers. In addition, higher levels of neutralizing antibody titers and T-cell immune responses were obtained using a homologous booster mRNA vaccine regimen of three different homologous or heterologous booster immunization strategies. Thus, this study provides assessment data to develop vaccine candidates and explore the effectiveness of the prime-boost approach.
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页数:11
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