Scientists provide therapeutic candidates for protection against JUNV infection
Junin virus (JUNV) is the pathogen of Argentine haemorrhagic fever which results in high lethality, while there is limited therapeutics available.
In a recent study from research group led by Prof. XIAO Gengfu in Wuhan Institute of Virology of the Chinese Academy of Sciences, a series of mAbs were isolated based on a newly established strategy, and five were proven to effectively neutralize JUNV. Further research has characterized their abilities of binding conformational GPC and affinities for GP1. Epitope mapping revealed that these nAbs might interact with loop 3 of GP1, and their common binding sites were identified to be contained in those previously reported. This study proved the feasibility of producing nAbs against full-length arenavirus GPC via DNA immunization and identified potential therapeutic candidates for AHF.
Finally, five mAbs were found to effectively neutralize JUNV. Further research indicated that they were capable of binding conformational GPC and strongly binding glycoprotein 1 which is responsible for receptor recognition. Epitope mapping revealed that they targeted loop 3 of GP1, and Tyr122 and Asp123 in loop 3 were identified as their common binding sites, which may account for their neutralizing activity.
Collectively, they have provided a new method for acquiring nAbs for pathogenic arenaviruses by screening antibodies against full-length GPC after immunization with DNA vectored with GPC gene. Moreover, five candidate nAbs were obtained, and their common epitopes were identified. Especially, loop 3 was hypothesized to be the most important domain for JUNV nAbs. This study provides therapeutic candidates against JUNV and clues to the discovery of new arenavirus vaccines and antibodies.
The results have been published in Antiviral Research entitled "Novel neutralizing monoclonal antibodies against Junin virus".
This study was funded by Natural Science Foundation of China and Open Research Fund Program of Wuhan National Bio-Safety Level 4 Lab of CAS, and supported by grants from the Chinese Academy of Sciences and the National Key Research and Development Program of China.
Figure 1. Neutralization of antibodies against Junin virus. Image by XIAO Gengfu
Figure 2. Epitope mapping of the five neutralizing antibodies. Image by XIAO Gengfu
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China (http://english.whiov.cas.cn/)