scholarly journals Bivalent vaccine platform based on Japanese encephalitis virus (JEV) elicits neutralizing antibodies against JEV and hepatitis C virus

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ryohei Saga ◽  
Akira Fujimoto ◽  
Noriyuki Watanabe ◽  
Mami Matsuda ◽  
Makoto Hasegawa ◽  
...  
2018 ◽  
Vol 93 (1) ◽  
Author(s):  
Dong-Rong Yi ◽  
Ni An ◽  
Zhen-Long Liu ◽  
Feng-Wen Xu ◽  
Kavita Raniga ◽  
...  

ABSTRACTType I interferon (IFN) inhibits viruses by inducing the expression of antiviral proteins. The IFN-induced myxovirus resistance B (MxB) protein has been reported to inhibit a limited number of viruses, including HIV-1 and herpesviruses, but its antiviral coverage remains to be explored further. Here we show that MxB interferes with RNA replication of hepatitis C virus (HCV) and significantly inhibits viral replication in a cyclophilin A (CypA)-dependent manner. Our data further show that MxB interacts with the HCV protein NS5A, thereby impairing NS5A interaction with CypA and NS5A localization to the endoplasmic reticulum, two events essential for HCV RNA replication. Interestingly, we found that MxB significantly inhibits two additional CypA-dependent viruses of theFlaviviridaefamily, namely, Japanese encephalitis virus and dengue virus, suggesting a potential link between virus dependence on CypA and virus susceptibility to MxB inhibition. Collectively, these data have identified MxB as a key factor behind IFN-mediated suppression of HCV infection, and they suggest that other CypA-dependent viruses may also be subjected to MxB restriction.IMPORTANCEViruses of theFlaviviridaefamily cause major illness and death around the world and thus pose a great threat to human health. Here we show that IFN-inducible MxB restricts several members of theFlaviviridae, including HCV, Japanese encephalitis virus, and dengue virus. This finding not only suggests an active role of MxB in combating these major pathogenic human viruses but also significantly expands the antiviral spectrum of MxB. Our study further strengthens the link between virus dependence on CypA and susceptibility to MxB restriction and also suggests that MxB may employ a common mechanism to inhibit different viruses. Elucidating the antiviral functions of MxB advances our understanding of IFN-mediated host antiviral defense and may open new avenues to the development of novel antiviral therapeutics.


Virology ◽  
2000 ◽  
Vol 273 (2) ◽  
pp. 316-324 ◽  
Author(s):  
Andi Utama ◽  
Hiroyuki Shimizu ◽  
Futoshi Hasebe ◽  
Kouichi Morita ◽  
Akira Igarashi ◽  
...  

2011 ◽  
Vol 5 (10) ◽  
pp. e1311 ◽  
Author(s):  
Kathryn B. Anderson ◽  
Robert V. Gibbons ◽  
Stephen J. Thomas ◽  
Alan L. Rothman ◽  
Ananda Nisalak ◽  
...  

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0147841 ◽  
Author(s):  
Eun Ju Lee ◽  
Go-Woon Cha ◽  
Young Ran Ju ◽  
Myung Guk Han ◽  
Won-Ja Lee ◽  
...  

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 81
Author(s):  
Sarah Honjo ◽  
Michiaki Masuda ◽  
Tomohiro Ishikawa

Japanese encephalitis virus (JEV) is classified into five genotypes labelled I through V. Although the genotype V (GV) JEV was originally found and had apparently been limited in Malaysia for more than 50 years, its emergence in Korea and China has recently been reported. Therefore, the GV JEV might be spreading over new geographical regions as a cause of potential public health problems. However, it is unknown whether the currently available JEV vaccines are effective against the emerging GV strains. To investigate this issue, a novel virus-like particle-based neutralizing assay was developed in this study. By using this assay, the inactivated JEV vaccine used in Japan and the recombinant sub-viral particles (SVPs) bearing the E protein of the GV Muar strain were characterized for the immunogenicity against the GV JEV. Although the inactivated vaccine alone failed to elicit a detectable level of neutralizing antibodies against the GV JEV, the vaccine added with the Muar-derived SVPs induced relatively high titers of neutralizing antibodies, associated with the efficient Th1 immune responses, against the GV JEV. The results indicate that addition of the GV JEV-derived antigens may be useful for developing the vaccine that is universally effective against JEV including the emerging GV strains.


2008 ◽  
Vol 82 (14) ◽  
pp. 7009-7021 ◽  
Author(s):  
Ana P. Goncalvez ◽  
Cheng-Hsin Chien ◽  
Kamolchanok Tubthong ◽  
Inna Gorshkova ◽  
Carrie Roll ◽  
...  

ABSTRACT Japanese encephalitis virus (JEV)-specific Fab antibodies were recovered by repertoire cloning from chimpanzees initially immunized with inactivated JE-VAX and then boosted with attenuated JEV SA14-14-2. From a panel of 11 Fabs recovered by different panning strategies, three highly potent neutralizing antibodies, termed Fabs A3, B2, and E3, which recognized spatially separated regions on the virion, were identified. These antibodies reacted with epitopes in different domains: the major determinant for Fab A3 was Lys179 (domain I), that for Fab B2 was Ile126 (domain II), and that for Fab E3 was Gly302 (domain III) in the envelope protein, suggesting that these antibodies neutralize the virus by different mechanisms. Potent neutralizing antibodies reacted with a low number of binding sites available on the virion. These three Fabs and derived humanized monoclonal antibodies (MAbs) exhibited high neutralizing activities against a broad spectrum of JEV genotype strains. Demonstration of antibody-mediated protection of JEV infection in vivo is provided using the mouse encephalitis model. MAb B2 was most potent, with a 50% protective dose (ED50) of 0.84 μg, followed by MAb A3 (ED50 of 5.8 μg) and then MAb E3 (ED50 of 24.7 μg) for a 4-week-old mouse. Administration of 200 μg/mouse of MAb B2 1 day after otherwise lethal JEV infection protected 50% of mice and significantly prolonged the average survival time compared to that of mice in the unprotected group, suggesting a therapeutic potential for use of MAb B2 in humans.


Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 980
Author(s):  
Muhammad Naveed Anwar ◽  
Chunying Jiang ◽  
Di Di ◽  
Junjie Zhang ◽  
Shuang Guo ◽  
...  

Virus-like particles (VLPs) are non-replicative vectors for the delivery of heterologous epitopes and are considered one of the most potent inducers of cellular and humoral immune responses in mice and guinea pigs. In the present study, VLP-JEVe was constructed by the insertion of six Japanese encephalitis virus (JEV) envelope protein epitopes into different surface loop regions of PPV VP2 by the substitution of specific amino acid sequences without altering the assembly of the virus; subsequently, the protective efficacy of this VLP-JEVe was evaluated against JEV challenge in mice and guinea pigs. Mice immunized with the VLP-JEVe antigen developed high titers of neutralizing antibodies and 100% protection against lethal JEV challenge. The neutralizing and hemagglutination inhibition (HI) antibody responses were also induced in guinea pigs vaccinated with VLP-JEVe. In addition, immunization with VLP-JEVe in mice induced effective neutralizing antibodies and protective immunity against PPV (porcine parvovirus) challenge in guinea pigs. These studies suggest that VLP-JEVe produced as described here could be a potential candidate for vaccine development.


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