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Massive production of efficacious SARS-CoV-2 vaccines is essential for controlling the ongoing COVID-19 pandemic. We report here the preclinical development of yeast-produced receptor-binding domain (RBD)-based recombinant protein SARS-CoV-2 vaccines. We found that monomeric RBD of SARS-CoV-2 could be efficiently produced as a secreted protein from transformed Pichia pastoris (P. pastoris) yeast. Yeast-derived RBD-monomer possessed functional conformation and was able to elicit protective level of neutralizing antibodies in mice. We further designed and expressed a genetically linked dimeric RBD protein in yeast. The engineered dimeric RBD was more potent than the monomeric RBD in inducing long-lasting neutralizing antibodies. Mice immunized with either monomeric RBD or dimeric RBD were effectively protected from live SARS-CoV-2 virus challenge even at 18 weeks after the last vaccine dose. Importantly, we found that the antisera raised against the RBD of a single SARS-CoV-2 prototype strain could effectively neutralize the two predominant circulating variants B.1.1.7 and B.1.351, implying broad-spectrum protective potential of the RBD-based vaccines. Our data demonstrate that yeast-derived RBD-based recombinant SARS-CoV-2 vaccines are feasible and efficacious, opening up a new avenue for rapid and cost-effective production of SARS-CoV-2 vaccines to achieve global immunization.
Jinkai Zang; Yuanfei Zhu; Yu Zhou; Chenjian Gu; Yufang Yi; Shuxia Wang; Shiqi Xu; Gaowei Hu; Shujuan Du; Yannan Yin; Yalei Wang; Yong Yang; Xueyang Zhang; Haikun Wang; Feifei Yin; Chao Zhang; Qiang Deng; Youhua Xie; Zhong Huang. Yeast-produced RBD-based recombinant protein vaccines elicit broadly neutralizing antibodies and durable protective immunity against SARS-CoV-2 infection. Cell Discovery 2021, 7, 1 .
AMA StyleJinkai Zang, Yuanfei Zhu, Yu Zhou, Chenjian Gu, Yufang Yi, Shuxia Wang, Shiqi Xu, Gaowei Hu, Shujuan Du, Yannan Yin, Yalei Wang, Yong Yang, Xueyang Zhang, Haikun Wang, Feifei Yin, Chao Zhang, Qiang Deng, Youhua Xie, Zhong Huang. Yeast-produced RBD-based recombinant protein vaccines elicit broadly neutralizing antibodies and durable protective immunity against SARS-CoV-2 infection. Cell Discovery. 2021; 7 ():1.
Chicago/Turabian StyleJinkai Zang; Yuanfei Zhu; Yu Zhou; Chenjian Gu; Yufang Yi; Shuxia Wang; Shiqi Xu; Gaowei Hu; Shujuan Du; Yannan Yin; Yalei Wang; Yong Yang; Xueyang Zhang; Haikun Wang; Feifei Yin; Chao Zhang; Qiang Deng; Youhua Xie; Zhong Huang. 2021. "Yeast-produced RBD-based recombinant protein vaccines elicit broadly neutralizing antibodies and durable protective immunity against SARS-CoV-2 infection." Cell Discovery 7, no. : 1.
The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most of the currently approved SARS-CoV-2 vaccines use the prototype strain-derived spike (S) protein or its receptor-binding domain (RBD) as the vaccine antigen. The emergence of several novel SARS-CoV-2 variants has raised concerns about potential immune escape. In this study, we performed an immunogenicity comparison of prototype strain-derived RBD, S1, and S ectodomain trimer (S-trimer) antigens and evaluated their induction of neutralizing antibodies against three circulating SARS-CoV-2 variants, including B.1.1.7, B.1.351, and B.1.617.1. We found that, at the same antigen dose, the RBD and S-trimer vaccines were more potent than the S1 vaccine in eliciting long-lasting, high-titer broadly neutralizing antibodies in mice. The RBD immune sera remained highly effective against the B.1.1.7, B.1.351, and B.1.617.1 variants despite the corresponding neutralizing titers decreasing by 1.2-, 2.8-, and 3.5-fold relative to that against the wild-type strain. Significantly, the S-trimer immune sera exhibited comparable neutralization potency (less than twofold variation in neutralizing GMTs) towards the prototype strain and all three variants tested. These findings provide valuable information for further development of recombinant protein-based SARS-CoV-2 vaccines and support the continued use of currently approved SARS-CoV-2 vaccines in the regions/countries where variant viruses circulate.
Yong Yang; Jinkai Zang; Shiqi Xu; Xueyang Zhang; Sule Yuan; Haikun Wang; Dimitri Lavillette; Chao Zhang; Zhong Huang. Elicitation of Broadly Neutralizing Antibodies against B.1.1.7, B.1.351, and B.1.617.1 SARS-CoV-2 Variants by Three Prototype Strain-Derived Recombinant Protein Vaccines. Viruses 2021, 13, 1421 .
AMA StyleYong Yang, Jinkai Zang, Shiqi Xu, Xueyang Zhang, Sule Yuan, Haikun Wang, Dimitri Lavillette, Chao Zhang, Zhong Huang. Elicitation of Broadly Neutralizing Antibodies against B.1.1.7, B.1.351, and B.1.617.1 SARS-CoV-2 Variants by Three Prototype Strain-Derived Recombinant Protein Vaccines. Viruses. 2021; 13 (8):1421.
Chicago/Turabian StyleYong Yang; Jinkai Zang; Shiqi Xu; Xueyang Zhang; Sule Yuan; Haikun Wang; Dimitri Lavillette; Chao Zhang; Zhong Huang. 2021. "Elicitation of Broadly Neutralizing Antibodies against B.1.1.7, B.1.351, and B.1.617.1 SARS-CoV-2 Variants by Three Prototype Strain-Derived Recombinant Protein Vaccines." Viruses 13, no. 8: 1421.
The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current SARS-CoV-2 vaccines are based on spike (S) protein, S1 subunit, or receptor-binding domain (RBD) of prototype strain. Emergence of several novel SARS-CoV-2 variants has raised concern about potential immune escape. In this study, we performed an immunogenicity comparison of ancestral RBD, S1, and S ectodomain trimer (S-trimer) antigens and tested the efficacy of these prototype vaccines against the circulating variants, especially B.1.617 that has been linked to India's current COVID-19 surge. We found that RBD and S-trimer proteins could induce significantly higher neutralizing antibody titers than S1 protein. For the three vaccines, the neutralizing titers decreased over time, but still remained high for at least five months after immunization. Importantly, the three prototype vaccines were still effective in neutralizing the variants of concern, although B.1.351 and B.1.617.1 lineages showed varying degrees of reduction in neutralization by the immune sera. The vaccines-induced sera were shown to block receptor binding and inhibit S protein-mediated membrane fusion. In addition, the immune sera did not promote antibody-dependent enhancement (ADE) in vitro. Our work provides valuable information for development of SARS-CoV-2 subunit vaccines and also supports the continued use of ancestral RBD or S-based vaccines to fight the COVID-19 epidemic.
Yong Yang; Jinkai Zang; Shiqi Xu; Xueyang Zhang; Sule Yuan; Dimitri Lavillette; Chao Zhang; Zhong Huang. Efficacy of ancestral receptor-binding domain, S1 and trimeric spike protein vaccines against SARS-CoV-2 variants B.1.1.7, B.1.351, and B.1.617.1. 2021, 1 .
AMA StyleYong Yang, Jinkai Zang, Shiqi Xu, Xueyang Zhang, Sule Yuan, Dimitri Lavillette, Chao Zhang, Zhong Huang. Efficacy of ancestral receptor-binding domain, S1 and trimeric spike protein vaccines against SARS-CoV-2 variants B.1.1.7, B.1.351, and B.1.617.1. . 2021; ():1.
Chicago/Turabian StyleYong Yang; Jinkai Zang; Shiqi Xu; Xueyang Zhang; Sule Yuan; Dimitri Lavillette; Chao Zhang; Zhong Huang. 2021. "Efficacy of ancestral receptor-binding domain, S1 and trimeric spike protein vaccines against SARS-CoV-2 variants B.1.1.7, B.1.351, and B.1.617.1." , no. : 1.
Enterovirus D68 (EV-D68) is an emerging pathogen associated with respiratory diseases and/or acute flaccid myelitis. Here, two MAbs, 2H12 and 8F12, raised against EV-D68 virus-like particle (VLP), show distinct preference in binding VLP and virion and in neutralizing different EV-D68 strains. A combination of 2H12 and 8F12 exhibits balanced and potent neutralization effects and confers broader protection in mice than single MAbs when given at onset of symptoms. Cryo-EM structures of EV-D68 virion complexed with 2H12 or 8F12 show that both antibodies bind to the canyon region of the virion, creating steric hindrance for sialic acid receptor binding. Additionally, 2H12 binding can impair virion integrity and trigger premature viral uncoating. We also capture an uncoating intermediate induced by 2H12 binding, not previously described for picornaviruses. Our study elucidates the structural basis and neutralizing mechanisms of the 2H12 and 8F12 MAbs and supports further development of the 2H12/8F12 cocktail as a broad-spectrum therapeutic agent against EV-D68 infections in humans.
Chao Zhang; Cong Xu; Wenlong Dai; Yifan Wang; Zhi Liu; Xueyang Zhang; Xuesong Wang; Haikun Wang; Sitang Gong; Yao Cong; Zhong Huang. Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections. Nature Communications 2021, 12, 1 -16.
AMA StyleChao Zhang, Cong Xu, Wenlong Dai, Yifan Wang, Zhi Liu, Xueyang Zhang, Xuesong Wang, Haikun Wang, Sitang Gong, Yao Cong, Zhong Huang. Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections. Nature Communications. 2021; 12 (1):1-16.
Chicago/Turabian StyleChao Zhang; Cong Xu; Wenlong Dai; Yifan Wang; Zhi Liu; Xueyang Zhang; Xuesong Wang; Haikun Wang; Sitang Gong; Yao Cong; Zhong Huang. 2021. "Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections." Nature Communications 12, no. 1: 1-16.
The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen–antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections.
Chao Zhang; Yifan Wang; Yuanfei Zhu; Caixuan Liu; Chenjian Gu; Shiqi Xu; Yalei Wang; Yu Zhou; Yanxing Wang; Wenyu Han; Xiaoyu Hong; Yong Yang; Xueyang Zhang; Tingfeng Wang; Cong Xu; Qin Hong; Shutian Wang; Qiaoyu Zhao; Weihua Qiao; Jinkai Zang; Liangliang Kong; Fangfang Wang; Haikun Wang; Di Qu; Dimitri Lavillette; Hong Tang; Qiang Deng; Youhua Xie; Yao Cong; Zhong Huang. Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections. Nature Communications 2021, 12, 1 -16.
AMA StyleChao Zhang, Yifan Wang, Yuanfei Zhu, Caixuan Liu, Chenjian Gu, Shiqi Xu, Yalei Wang, Yu Zhou, Yanxing Wang, Wenyu Han, Xiaoyu Hong, Yong Yang, Xueyang Zhang, Tingfeng Wang, Cong Xu, Qin Hong, Shutian Wang, Qiaoyu Zhao, Weihua Qiao, Jinkai Zang, Liangliang Kong, Fangfang Wang, Haikun Wang, Di Qu, Dimitri Lavillette, Hong Tang, Qiang Deng, Youhua Xie, Yao Cong, Zhong Huang. Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections. Nature Communications. 2021; 12 (1):1-16.
Chicago/Turabian StyleChao Zhang; Yifan Wang; Yuanfei Zhu; Caixuan Liu; Chenjian Gu; Shiqi Xu; Yalei Wang; Yu Zhou; Yanxing Wang; Wenyu Han; Xiaoyu Hong; Yong Yang; Xueyang Zhang; Tingfeng Wang; Cong Xu; Qin Hong; Shutian Wang; Qiaoyu Zhao; Weihua Qiao; Jinkai Zang; Liangliang Kong; Fangfang Wang; Haikun Wang; Di Qu; Dimitri Lavillette; Hong Tang; Qiang Deng; Youhua Xie; Yao Cong; Zhong Huang. 2021. "Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections." Nature Communications 12, no. 1: 1-16.
Human noroviruses are the dominant causative agent of acute viral gastroenteritis worldwide. During the winter of 2014-2015, genotype GII.17 cluster IIIb strains emerged as the leading cause of norovirus infection in Asia and later spread to other parts of the world. It is speculated that mutation at blockade epitopes may have resulted in virus escape from herd immunity, leading to the emergence of GII.17 cluster IIIb variants. Here we identify a GII.17 cluster IIIb-specific blockade epitope by monoclonal antibody (mAb)-based epitope mapping. Four mAbs (designated as M1 to M4) were generated from mice immunized with virus-like particle (VLP) of a GII.17 cluster IIIb strain. Among them, M1 and M3 reacted specifically with the cluster IIIb VLP but not with the VLPs from clusters II or IIIa. Moreover, M1 and M3 dose-dependently blocked cluster IIIb VLP binding with its ligand, histo-blood group antigens (HBGAs). Epitope mapping revealed that M1 and M3 recognized the same highly exposed epitope consisting of residues 293-296 and 299 in the capsid protein VP1. Sequence alignment showed that the M1/M3 epitope sequence is highly variable among different GII.17 clusters whereas it is identical for cluster IIIIb strains. These data define a dominant blockade epitope of GII.17 norovirus and provide evidence that blockade epitope evolution contributes to the emergence of GII.17 cluster IIIb strains.
Yufang Yi; Xiaoli Wang; Shuxia Wang; Pei Xiong; Qingwei Liu; Chao Zhang; Feifei Yin; Zhong Huang. Identification of a blockade epitope of human norovirus GII.17. Emerging Microbes & Infections 2021, 10, 954 -963.
AMA StyleYufang Yi, Xiaoli Wang, Shuxia Wang, Pei Xiong, Qingwei Liu, Chao Zhang, Feifei Yin, Zhong Huang. Identification of a blockade epitope of human norovirus GII.17. Emerging Microbes & Infections. 2021; 10 (1):954-963.
Chicago/Turabian StyleYufang Yi; Xiaoli Wang; Shuxia Wang; Pei Xiong; Qingwei Liu; Chao Zhang; Feifei Yin; Zhong Huang. 2021. "Identification of a blockade epitope of human norovirus GII.17." Emerging Microbes & Infections 10, no. 1: 954-963.
The recent outbreaks of SARS-CoV-2 pose a global health emergency. The SARS-CoV-2 trimeric spike (S) glycoprotein interacts with the human ACE2 receptor to mediate viral entry into host cells. We report the cryo-EM structures of a tightly closed SARS-CoV-2 S trimer with packed fusion peptide and an ACE2-bound S trimer at 2.7- and 3.8-Å resolution, respectively. Accompanying ACE2 binding to the up receptor-binding domain (RBD), the associated ACE2-RBD exhibits continuous swing motions. Notably, the SARS-CoV-2 S trimer appears much more sensitive to the ACE2 receptor than the SARS-CoV S trimer regarding receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2. Our findings depict the mechanism of ACE2-induced S trimer conformational transitions from the ground prefusion state toward the postfusion state, facilitating development of anti–SARS-CoV-2 vaccines and therapeutics.
Cong Xu; Yanxing Wang; Caixuan Liu; Chao Zhang; Wenyu Han; Xiaoyu Hong; Yifan Wang; Qin Hong; Shutian Wang; Qiaoyu Zhao; Yalei Wang; Yong Yang; Kaijian Chen; Wei Zheng; Liangliang Kong; Fangfang Wang; Qinyu Zuo; Zhong Huang; Yao Cong. Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM. Science Advances 2020, 7, eabe5575 .
AMA StyleCong Xu, Yanxing Wang, Caixuan Liu, Chao Zhang, Wenyu Han, Xiaoyu Hong, Yifan Wang, Qin Hong, Shutian Wang, Qiaoyu Zhao, Yalei Wang, Yong Yang, Kaijian Chen, Wei Zheng, Liangliang Kong, Fangfang Wang, Qinyu Zuo, Zhong Huang, Yao Cong. Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM. Science Advances. 2020; 7 (1):eabe5575.
Chicago/Turabian StyleCong Xu; Yanxing Wang; Caixuan Liu; Chao Zhang; Wenyu Han; Xiaoyu Hong; Yifan Wang; Qin Hong; Shutian Wang; Qiaoyu Zhao; Yalei Wang; Yong Yang; Kaijian Chen; Wei Zheng; Liangliang Kong; Fangfang Wang; Qinyu Zuo; Zhong Huang; Yao Cong. 2020. "Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM." Science Advances 7, no. 1: eabe5575.
Jinkai Zang; Chenjian Gu; Bingjie Zhou; Chao Zhang; Yong Yang; Shiqi Xu; Lulu Bai; Rong Zhang; Qiang Deng; Zhenghong Yuan; Hong Tang; Di Qu; Dimitri Lavillette; Youhua Xie; Zhong Huang. Immunization with the receptor-binding domain of SARS-CoV-2 elicits antibodies cross-neutralizing SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement. Cell Discovery 2020, 6, 1 -4.
AMA StyleJinkai Zang, Chenjian Gu, Bingjie Zhou, Chao Zhang, Yong Yang, Shiqi Xu, Lulu Bai, Rong Zhang, Qiang Deng, Zhenghong Yuan, Hong Tang, Di Qu, Dimitri Lavillette, Youhua Xie, Zhong Huang. Immunization with the receptor-binding domain of SARS-CoV-2 elicits antibodies cross-neutralizing SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement. Cell Discovery. 2020; 6 (1):1-4.
Chicago/Turabian StyleJinkai Zang; Chenjian Gu; Bingjie Zhou; Chao Zhang; Yong Yang; Shiqi Xu; Lulu Bai; Rong Zhang; Qiang Deng; Zhenghong Yuan; Hong Tang; Di Qu; Dimitri Lavillette; Youhua Xie; Zhong Huang. 2020. "Immunization with the receptor-binding domain of SARS-CoV-2 elicits antibodies cross-neutralizing SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement." Cell Discovery 6, no. 1: 1-4.
Enterovirus D68 (EV-D68) is an emerging pathogen associated with respiratory diseases and/or acute flaccid myelitis. Here, two MAbs, 2H12 and 8F12, raised against EV-D68 virus-like particle (VLP), showed distinct preference in binding VLP and virion and in neutralizing different strains. The 2H12/8F12 cocktail exhibited balanced and potent neutralization effects and conferred broader protection in mice than single MAbs when given at onset of symptoms. Cryo-EM structures of EV-D68 virion complexed with 2H12 or 8F12 showed that both antibodies bind to south rim of the canyon and obscure the canyon, blocking virus–cell binding. Additionally, 2H12 binding could partially impair virions and trigger uncoating, resulting in premature viral RNA release. We also captured an uncoating intermediate induced by 2H12 binding, not detected before in picornaviruses. Our study elucidates neutralizing mechanisms of the MAbs and supports further development of the 2H12/8F12 cocktail as a broad-spectrum therapeutic agent against EV-D68 infections in humans.
Zhong Huang; Chao Zhang; Cong Xu; Wenlong Dai; Yifan Wang; Zhi Liu; Xueyang Zhang; Xuesong Wang; Sitang Gong; Yao Cong. Development and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections. 2020, 1 .
AMA StyleZhong Huang, Chao Zhang, Cong Xu, Wenlong Dai, Yifan Wang, Zhi Liu, Xueyang Zhang, Xuesong Wang, Sitang Gong, Yao Cong. Development and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections. . 2020; ():1.
Chicago/Turabian StyleZhong Huang; Chao Zhang; Cong Xu; Wenlong Dai; Yifan Wang; Zhi Liu; Xueyang Zhang; Xuesong Wang; Sitang Gong; Yao Cong. 2020. "Development and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections." , no. : 1.
The recent outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid international spread pose a global health emergency. The trimeric spike (S) glycoprotein interacts with its receptor human ACE2 to mediate viral entry into host-cells. Here we present cryo-EM structures of an uncharacterized tightly closed SARS-CoV-2 S-trimer and the ACE2-bound-S-trimer at 2.7-Å and 3.8-Å-resolution, respectively. The tightly closed S-trimer with inactivated fusion peptide may represent the ground prefusion state. ACE2 binding to the up receptor-binding domain (RBD) within S-trimer triggers continuous swing-motions of ACE2-RBD, resulting in conformational dynamics of S1 subunits. Noteworthy, SARS-CoV-2 S-trimer appears much more sensitive to ACE2-receptor than SARS-CoV S-trimer in terms of receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and residue Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2, and provided structural basis of the spike D614G-mutation induced enhanced infectivity. Our findings offer a thorough picture on the mechanism of ACE2-induced conformational transitions of S-trimer from ground prefusion state towards postfusion state, thereby providing important information for development of vaccines and therapeutics aimed to block receptor binding.
Cong Xu; Yanxing Wang; Caixuan Liu; Chao Zhang; Wenyu Han; Xiaoyu Hong; Yifan Wang; Qin Hong; Shutian Wang; Qiaoyu Zhao; Yalei Wang; Yong Yang; Kaijian Chen; Wei Zheng; Liangliang Kong; Fangfang Wang; Qinyu Zuo; Zhong Huang; Yao Cong. Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM. 2020, 1 .
AMA StyleCong Xu, Yanxing Wang, Caixuan Liu, Chao Zhang, Wenyu Han, Xiaoyu Hong, Yifan Wang, Qin Hong, Shutian Wang, Qiaoyu Zhao, Yalei Wang, Yong Yang, Kaijian Chen, Wei Zheng, Liangliang Kong, Fangfang Wang, Qinyu Zuo, Zhong Huang, Yao Cong. Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM. . 2020; ():1.
Chicago/Turabian StyleCong Xu; Yanxing Wang; Caixuan Liu; Chao Zhang; Wenyu Han; Xiaoyu Hong; Yifan Wang; Qin Hong; Shutian Wang; Qiaoyu Zhao; Yalei Wang; Yong Yang; Kaijian Chen; Wei Zheng; Liangliang Kong; Fangfang Wang; Qinyu Zuo; Zhong Huang; Yao Cong. 2020. "Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM." , no. : 1.
Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. Currently, there is no vaccine available for preventing SARS-CoV-2 infection. Like closely related severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 also uses its receptor-binding domain (RBD) on the spike (S) protein to engage the host receptor, human angiotensin-converting enzyme 2 (ACE2), facilitating subsequent viral entry. Here we report the immunogenicity and vaccine potential of SARS-CoV-2 RBD (SARS2-RBD)-based recombinant proteins. Immunization with SARS2-RBD recombinant proteins potently induced a multi-functional antibody response in mice. The resulting antisera could efficiently block the interaction between SARS2-RBD and ACE2, inhibit S-mediated cell-cell fusion, and neutralize both SARS-CoV-2 pseudovirus entry and authentic SARS-CoV-2 infection. In addition, the anti-RBD sera also exhibited cross binding, ACE2-blockade, and neutralization effects towards SARS-CoV. More importantly, we found that the anti-RBD sera did not promote antibody-dependent enhancement of either SARS-CoV-2 pseudovirus entry or authentic virus infection of Fc receptor-bearing cells. These findings provide a solid foundation for developing RBD-based subunit vaccines for SARS-CoV2.
Jinkai Zang; Chenjian Gu; Bingjie Zhou; Chao Zhang; Yong Yang; Shiqi Xu; Xueyang Zhang; Yu Zhou; Lulu Bai; Yang Wu; Zhiping Sun; Rong Zhang; Qiang Deng; Zhenghong Yuan; Hong Tang; Di Qu; Dimitri Lavillette; Youhua Xie; Zhong Huang. Immunization with the receptor–binding domain of SARS-CoV-2 elicits antibodies cross-neutralizing SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement. 2020, 1 .
AMA StyleJinkai Zang, Chenjian Gu, Bingjie Zhou, Chao Zhang, Yong Yang, Shiqi Xu, Xueyang Zhang, Yu Zhou, Lulu Bai, Yang Wu, Zhiping Sun, Rong Zhang, Qiang Deng, Zhenghong Yuan, Hong Tang, Di Qu, Dimitri Lavillette, Youhua Xie, Zhong Huang. Immunization with the receptor–binding domain of SARS-CoV-2 elicits antibodies cross-neutralizing SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement. . 2020; ():1.
Chicago/Turabian StyleJinkai Zang; Chenjian Gu; Bingjie Zhou; Chao Zhang; Yong Yang; Shiqi Xu; Xueyang Zhang; Yu Zhou; Lulu Bai; Yang Wu; Zhiping Sun; Rong Zhang; Qiang Deng; Zhenghong Yuan; Hong Tang; Di Qu; Dimitri Lavillette; Youhua Xie; Zhong Huang. 2020. "Immunization with the receptor–binding domain of SARS-CoV-2 elicits antibodies cross-neutralizing SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement." , no. : 1.
Zika virus (ZIKV) infection poses a serious threat to human health. However, no licensed vaccine or therapeutic drug is currently available for ZIKV. We have previously shown that recombinant ZIKV E80 protein induced potent neutralizing antibody response and protected mice from lethal viral challenge. In the present study, we isolated five ZIKV neutralizing monoclonal antibodies (mAbs) from E80-immunized mice. These five mAbs specifically bound and neutralized Asian-lineage ZIKV strains. Epitope mapping revealed that all of the five mAbs recognized a novel linear epitope located on the glycan loop of E protein domain I. Sequence alignment revealed that the epitope was extremely conserved in ZIKV but highly variable between ZIKV and other flaviviruses. Thus, these five mAbs form a new class of anti-ZIKV antibodies exhibiting broad-spectrum neutralization on Asian-lineage ZIKV. A representative of this mAb class, 5F8, was found to exert inhibitory function in vitro primarily at the early stage of the post-attachment viral entry process. Importantly, mAb 5F8 was able to confer full protection in a mouse model of ZIKV lethal infection. Our results have strong implications for developing anti-ZIKV vaccines and therapeutic mAbs.
Panke Qu; Chao Zhang; Min Li; Weimin Ma; Pei Xiong; Qingwei Liu; Gang Zou; Dimitri Lavillette; Feifei Yin; Xia Jin; Zhong Huang. A new class of broadly neutralizing antibodies that target the glycan loop of Zika virus envelope protein. Cell Discovery 2020, 6, 1 -14.
AMA StylePanke Qu, Chao Zhang, Min Li, Weimin Ma, Pei Xiong, Qingwei Liu, Gang Zou, Dimitri Lavillette, Feifei Yin, Xia Jin, Zhong Huang. A new class of broadly neutralizing antibodies that target the glycan loop of Zika virus envelope protein. Cell Discovery. 2020; 6 (1):1-14.
Chicago/Turabian StylePanke Qu; Chao Zhang; Min Li; Weimin Ma; Pei Xiong; Qingwei Liu; Gang Zou; Dimitri Lavillette; Feifei Yin; Xia Jin; Zhong Huang. 2020. "A new class of broadly neutralizing antibodies that target the glycan loop of Zika virus envelope protein." Cell Discovery 6, no. 1: 1-14.
Enterovirus 71 (EV71) is the main causative agent of severe hand-foot-mouth disease. EV71 affects countries mainly in the Asia-Pacific region, which makes it unattractive for pharmaceutical companies to develop drugs or vaccine to combat EV71 infection. However, development of these drugs and vaccines is vital to protect younger generations. This study aims to develop a specific monoclonal antibody (mAb) to EV71 using a plant platform, which is a cost-effective and scalable production technology. A previous report showed that D5, a murine anti-EV71 mAb, binds to VP1 protein of EV71, potently neutralizes EV71 in vitro, and effectively protects mice against EV71 infection. Herein, plant-produced chimeric D5 (cD5) mAb, variable regions of murine D5 antibody linked with constant regions of human IgG1, was transiently expressed in Nicotiana benthamiana using geminiviral vectors. The antibody was expressed at high levels within six days of infiltration. Plant-produced cD5 retained its in vitro high-affinity binding and neutralizing activity against EV71. Furthermore, a single dose (10 µg/g body weight) of plant-produced cD5 mAb offered 100% protection against infection in mice after a lethal EV71 challenge. Therefore, our results showed that plant-produced anti-EV71 mAb is an effective, safe, and affordable therapeutic option against EV71 infection.
Kaewta Rattanapisit; Zhang Chao; Konlavat Siriwattananon; Zhong Huang; Waranyoo Phoolcharoen. Plant-Produced Anti-Enterovirus 71 (EV71) Monoclonal Antibody Efficiently Protects Mice Against EV71 Infection. Plants 2019, 8, 560 .
AMA StyleKaewta Rattanapisit, Zhang Chao, Konlavat Siriwattananon, Zhong Huang, Waranyoo Phoolcharoen. Plant-Produced Anti-Enterovirus 71 (EV71) Monoclonal Antibody Efficiently Protects Mice Against EV71 Infection. Plants. 2019; 8 (12):560.
Chicago/Turabian StyleKaewta Rattanapisit; Zhang Chao; Konlavat Siriwattananon; Zhong Huang; Waranyoo Phoolcharoen. 2019. "Plant-Produced Anti-Enterovirus 71 (EV71) Monoclonal Antibody Efficiently Protects Mice Against EV71 Infection." Plants 8, no. 12: 560.
Zika virus (ZIKV) infection is a serious public health concern due to its ability to induce neurological defects and its potential for rapid transmission at a global scale. However, no vaccine is currently available to prevent ZIKV infection. Here, we report the development of a yeast-derived subunit protein vaccine for ZIKV. The envelope protein domain III (EDIII) of ZIKV was produced as a secretory protein in the yeast Pichia pastoris. The yeast-derived EDIII could inhibit ZIKV infection in vitro in a dose-dependent manner, suggesting that it had acquired an appropriate conformation to bind to cellular receptors of ZIKV. Immunization with recombinant EDIII protein effectively induced antigen-specific binding antibodies and cellular immune responses. The resulting anti-EDIII sera could efficiently neutralize ZIKV representative strains from both Asian and African lineages. Passive transfer with the anti-EDIII neutralizing sera could confer protection against lethal ZIKV challenge in mice. Importantly, we found that purified anti-EDIII antibodies did not cross-react with closely related dengue virus (DENV) and therefore did not enhance DENV infection. Collectively, our results demonstrate that yeast-produced EDIII is a safe and effective ZIKV vaccine candidate.
Wei Zhang; Panke Qu; Dapeng Li; Chao Zhang; Qingwei Liu; Gang Zou; Myrielle Dupont-Rouzeyrol; Dimitri Lavillette; Xia Jin; Feifei Yin; Zhong Huang. Yeast-produced subunit protein vaccine elicits broadly neutralizing antibodies that protect mice against Zika virus lethal infection. Antiviral Research 2019, 170, 104578 .
AMA StyleWei Zhang, Panke Qu, Dapeng Li, Chao Zhang, Qingwei Liu, Gang Zou, Myrielle Dupont-Rouzeyrol, Dimitri Lavillette, Xia Jin, Feifei Yin, Zhong Huang. Yeast-produced subunit protein vaccine elicits broadly neutralizing antibodies that protect mice against Zika virus lethal infection. Antiviral Research. 2019; 170 ():104578.
Chicago/Turabian StyleWei Zhang; Panke Qu; Dapeng Li; Chao Zhang; Qingwei Liu; Gang Zou; Myrielle Dupont-Rouzeyrol; Dimitri Lavillette; Xia Jin; Feifei Yin; Zhong Huang. 2019. "Yeast-produced subunit protein vaccine elicits broadly neutralizing antibodies that protect mice against Zika virus lethal infection." Antiviral Research 170, no. : 104578.
Coxsackievirus A10 (CV-A10) belongs to the Enterovirus species A and is a causative agent of hand, foot, and mouth disease. Here we present cryo-EM structures of CV-A10 mature virion and native empty particle (NEP) at 2.84 and 3.12 Å, respectively. Our CV-A10 mature virion structure reveals a density corresponding to a lipidic pocket factor of 18 carbon atoms in the hydrophobic pocket formed within viral protein 1. By structure-guided high-throughput drug screening and subsequent verification in cell-based infection-inhibition assays, we identified four compounds that inhibited CV-A10 infection in vitro. These compounds represent a new class of anti-enteroviral drug leads. Notably, one of the compounds, ICA135, also exerted broad-spectrum inhibitory effects on a number of representative viruses from all four species (A–D) of human enteroviruses. Our findings should facilitate the development of broadly effective drugs and vaccines for enterovirus infections.
Jinhuan Chen; Xiaohua Ye; Xue-Yang Zhang; Zhengdan Zhu; Xiang Zhang; Zhijian Xu; Zhanyu Ding; Gang Zou; Qingwei Liu; Liangliang Kong; Wen Jiang; Weiliang Zhu; Yao Cong; Zhong Huang. Coxsackievirus A10 atomic structure facilitating the discovery of a broad-spectrum inhibitor against human enteroviruses. Cell Discovery 2019, 5, 1 -15.
AMA StyleJinhuan Chen, Xiaohua Ye, Xue-Yang Zhang, Zhengdan Zhu, Xiang Zhang, Zhijian Xu, Zhanyu Ding, Gang Zou, Qingwei Liu, Liangliang Kong, Wen Jiang, Weiliang Zhu, Yao Cong, Zhong Huang. Coxsackievirus A10 atomic structure facilitating the discovery of a broad-spectrum inhibitor against human enteroviruses. Cell Discovery. 2019; 5 (1):1-15.
Chicago/Turabian StyleJinhuan Chen; Xiaohua Ye; Xue-Yang Zhang; Zhengdan Zhu; Xiang Zhang; Zhijian Xu; Zhanyu Ding; Gang Zou; Qingwei Liu; Liangliang Kong; Wen Jiang; Weiliang Zhu; Yao Cong; Zhong Huang. 2019. "Coxsackievirus A10 atomic structure facilitating the discovery of a broad-spectrum inhibitor against human enteroviruses." Cell Discovery 5, no. 1: 1-15.
Hand, foot, and mouth disease (HFMD) is an infectious disease that mainly affects infants and children, causing considerable morbidity and mortality worldwide. HFMD is commonly caused by enterovirus 71 (EV71) and coxsackieviruses A16 (CVA16), A6 (CVA6), and A10 (CVA10). Formalin-inactivated EV71 vaccines are currently available in China; however, these vaccines fail to confer cross-protection against infections by other HFMD-causing enteroviruses, highlighting the necessity of developing a multivalent HFMD vaccine. Our previous studies demonstrated that recombinant virus-like particles (VLP) of EV71, CVA16, and CVA6 are capable of inducing protective immunity against homologous virus challenges in mice. In this study, we generated CVA10-VLP using a baculovirus-insect cell expression system and then combined CVA10-VLP with EV71-VLP, CVA16-VLP, and CVA6-VLP to formulate a tetravalent VLP vaccine. Immunogenicity and protective efficacy of tetravalent VLP vaccine was compared with that of monovalent VLP vaccines. Mouse immunization studies revealed that the tetravalent vaccine elicited antigen-specific and long-lasting serum antibody responses comparable to those elicited by its corresponding monovalent vaccines. Moreover, tetravalent vaccine immune sera strongly neutralized EV71, CVA16, CVA10, and CVA6 strains with neutralization titers similar to those of their monovalent counterparts, indicating a good compatibility among the four antigens in the combination vaccine. Importantly, passively transferred tetravalent vaccine-immunized sera conferred efficient protection against single or mixed infections with EV71, CVA16, CVA10, and CVA6 viruses in mice, whereas the monovalent vaccines could only protect mice against homotypic virus infections but not heterotypic challenges. These results demonstrate that the tetravalent VLP vaccine represents a promising broad-spectrum HFMD vaccine candidate.
Wei Zhang; Wenlong Dai; Chao Zhang; Yu Zhou; Pei Xiong; Shuxia Wang; Xiaohua Ye; Qingwei Liu; Dongming Zhou; Zhong Huang. A virus-like particle-based tetravalent vaccine for hand, foot, and mouth disease elicits broad and balanced protective immunity. Emerging Microbes & Infections 2018, 7, 1 -12.
AMA StyleWei Zhang, Wenlong Dai, Chao Zhang, Yu Zhou, Pei Xiong, Shuxia Wang, Xiaohua Ye, Qingwei Liu, Dongming Zhou, Zhong Huang. A virus-like particle-based tetravalent vaccine for hand, foot, and mouth disease elicits broad and balanced protective immunity. Emerging Microbes & Infections. 2018; 7 (1):1-12.
Chicago/Turabian StyleWei Zhang; Wenlong Dai; Chao Zhang; Yu Zhou; Pei Xiong; Shuxia Wang; Xiaohua Ye; Qingwei Liu; Dongming Zhou; Zhong Huang. 2018. "A virus-like particle-based tetravalent vaccine for hand, foot, and mouth disease elicits broad and balanced protective immunity." Emerging Microbes & Infections 7, no. 1: 1-12.
Infection with Zika virus (ZIKV) may lead to severe neurologic disorders. It is of significant importance and urgency to develop safe and effective vaccines to prevent ZIKV infection. Here we report the development of ZIKV subunit vaccines based on insect cell-produced recombinant proteins. The N-terminal approximately 80% region (designated as E80) and the domain III (designated as EDIII) of ZIKV envelope (E) protein were efficiently produced as secreted proteins in a Drosophila S2 cell expression system. Both E80 and EDIII could inhibit ZIKV infection in vitro, suggesting that they may have folded properly to display native conformations. Immunization studies demonstrated that both E80 and EDIII vaccines were able to trigger antigen-specific antibody and T-cell responses in mice. The resulting anti-E80 and anti-EDIII sera could potently neutralize ZIKV infection in vitro. More importantly, passive transfer of either anti-E80 or anti-EDIII sera protected recipient mice against lethal ZIKV challenge. It is worth noting that the anti-EDIII sera possessed higher neutralizing titers and conferred more complete protection than the anti-E80 sera, indicating that the S2 cell-produced EDIII is a superior ZIKV vaccine candidate compared with the E80. These data support further preclinical and clinical development of a ZIKV subunit vaccine based on S2 cell-produced EDIII.
Panke Qu; Wei Zhang; Dapeng Li; Chao Zhang; Qingwei Liu; Xueyang Zhang; Xuesong Wang; Wenlong Dai; Yongfen Xu; Qibin Leng; Jin Zhong; Xia Jin; Zhong Huang. Insect cell-produced recombinant protein subunit vaccines protect against Zika virus infection. Antiviral Research 2018, 154, 97 -103.
AMA StylePanke Qu, Wei Zhang, Dapeng Li, Chao Zhang, Qingwei Liu, Xueyang Zhang, Xuesong Wang, Wenlong Dai, Yongfen Xu, Qibin Leng, Jin Zhong, Xia Jin, Zhong Huang. Insect cell-produced recombinant protein subunit vaccines protect against Zika virus infection. Antiviral Research. 2018; 154 ():97-103.
Chicago/Turabian StylePanke Qu; Wei Zhang; Dapeng Li; Chao Zhang; Qingwei Liu; Xueyang Zhang; Xuesong Wang; Wenlong Dai; Yongfen Xu; Qibin Leng; Jin Zhong; Xia Jin; Zhong Huang. 2018. "Insect cell-produced recombinant protein subunit vaccines protect against Zika virus infection." Antiviral Research 154, no. : 97-103.
Coxsackievirus A10 (CVA10) has emerged worldwide as one of the main pathogens of hand, foot, and mouth disease (HFMD) in recent years. However, there is currently no commercial vaccine available to prevent CVA10 infection. Here we report the development of a recombinant virus-like particle (VLP) based candidate vaccine for CVA10. Co-expression of the capsid protein precursor P1 and the protease 3CD of CVA10 in Pichia pastoris resulted in cleavage of P1 into three capsid subunit proteins VP0, VP1, and VP3. These three subunit proteins co-assembled into CVA10 VLPs, which were visualized as spherical particles with a diameter of ∼30 nm under electron microscope. Immunization studies showed that CVA10 VLP could efficiently induce antigen-specific serum antibodies in mice. The anti-VLP sera were able to potently neutralize homologous and heterologous CVA10 strains. Importantly, passively transferred anti-VLP sera fully protected recipient neonatal mice from lethal CVA10 infection. In addition, neonatal mice born to the VLP-immunized dams were also completely protected from CVA10 lethal challenge. Collectively, these data show that CVA10 VLP represents a promising CVA10 vaccine candidate.
Yu Zhou; Chao Zhang; Qingwei Liu; Sitang Gong; Lanlan Geng; Zhong Huang. A virus-like particle vaccine protects mice against coxsackievirus A10 lethal infection. Antiviral Research 2018, 152, 124 -130.
AMA StyleYu Zhou, Chao Zhang, Qingwei Liu, Sitang Gong, Lanlan Geng, Zhong Huang. A virus-like particle vaccine protects mice against coxsackievirus A10 lethal infection. Antiviral Research. 2018; 152 ():124-130.
Chicago/Turabian StyleYu Zhou; Chao Zhang; Qingwei Liu; Sitang Gong; Lanlan Geng; Zhong Huang. 2018. "A virus-like particle vaccine protects mice against coxsackievirus A10 lethal infection." Antiviral Research 152, no. : 124-130.
In recent years, enterovirus D68 (EVD68) has been reported increasingly to be associated with severe respiratory tract infections and acute flaccid myelitis (AFM) in children all over the world. Yet, no effective vaccines or antiviral drugs are currently available for EVD68. Although several experimental animal models have been developed, immunogenicity and protective efficacy of inactivated EVD68 vaccines has not been fully evaluated. To promote the development of vaccines, we established an Institute of Cancer Research (ICR) suckling mouse model of EVD68 infection in this study. The results showed that ICR neonatal mice up to about nine days of age were susceptible to infection with EVD68 clinical strain US/MO/14-18947 by intraperitoneal injection. The infected mice exhibited progressive limb paralysis prior to death and the mortality of mice was age- and virus dose-dependent. Tissue viral load analysis showed that limb muscle and spinal cord were the major sites of viral replication. Moreover, histopathologic examination revealed the severe necrosis of the limb and juxtaspinal muscles, suggesting that US/MO/14-18947 has a strong tropism toward muscle tissues. Additionally, β-propiolactone-inactivated EVD68 vaccine showed high purity and quality and induced robust EVD68-specific neutralizing antibody responses in adult mice. Importantly, results from both antisera transfer and maternal immunization experiments clearly showed that inactivated EVD68 vaccine was able to protect against lethal viral infection in the mouse model. In short, these results demonstrate the successful establishment of the mouse model of EVD68 infection for evaluating candidate vaccines against EVD68 and also provide important information for the development of inactivated virus-based EVD68 vaccines.
Chao Zhang; Xueyang Zhang; Wenlong Dai; Qingwei Liu; Pei Xiong; Shuxia Wang; Lanlan Geng; Sitang Gong; Zhong Huang. A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine. Viruses 2018, 10, 58 .
AMA StyleChao Zhang, Xueyang Zhang, Wenlong Dai, Qingwei Liu, Pei Xiong, Shuxia Wang, Lanlan Geng, Sitang Gong, Zhong Huang. A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine. Viruses. 2018; 10 (2):58.
Chicago/Turabian StyleChao Zhang; Xueyang Zhang; Wenlong Dai; Qingwei Liu; Pei Xiong; Shuxia Wang; Lanlan Geng; Sitang Gong; Zhong Huang. 2018. "A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine." Viruses 10, no. 2: 58.
Coxsackievirus A6 (CVA6) has recently emerged as one of the predominant causative agents of hand, foot, and mouth disease (HFMD). The structure of the CVA6 mature viral particle has not been solved thus far. Our previous work shows that recombinant virus-like particles (VLPs) of CVA6 represent a promising CVA6 vaccine candidate. Here, we report the first cryo-electron microscopy (cryo-EM) structure of the CVA6 VLP at 3.0-Å resolution. The CVA6 VLP exhibits the characteristic features of enteroviruses but presents an open channel at the 2-fold axis and an empty, collapsed VP1 pocket, which is broadly similar to the structures of the enterovirus 71 (EV71) VLP and coxsackievirus A16 (CVA16) 135S expanded particle, indicating that the CVA6 VLP is in an expanded conformation. Structural comparisons reveal that two common salt bridges within protomers are maintained in the CVA6 VLP and other viruses of the Enterovirus genus, implying that these salt bridges may play a critical role in enteroviral protomer assembly. However, there are apparent structural differences among the CVA6 VLP, EV71 VLP, and CVA16 135S particle in the surface-exposed loops and C termini of subunit proteins, which are often antigenic sites for enteroviruses. By immunological assays, we identified two CVA6-specific linear B-cell epitopes (designated P42 and P59) located at the GH loop and the C-terminal region of VP1, respectively, in agreement with the structure-based prediction of antigenic sites. Our findings elucidate the structural basis and important antigenic sites of the CVA6 VLP as a strong vaccine candidate and also provide insight into enteroviral protomer assembly. IMPORTANCE Coxsackievirus A6 (CVA6) is becoming one of the major pathogens causing hand, foot, and mouth disease (HFMD), leading to significant morbidity and mortality in children and adults. However, no vaccine is currently available to prevent CVA6 infection. Our previous work shows that recombinant virus-like particles (VLPs) of CVA6 are a promising CVA6 vaccine candidate. Here, we present a 3.0-Å structure of the CVA6 VLP determined by cryo-electron microscopy. The overall architecture of the CVA6 VLP is similar to those of the expanded structures of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), but careful structural comparisons reveal significant differences in the surface-exposed loops and C termini of each capsid protein of these particles. In addition, we identified two CVA6-specific linear B-cell epitopes and mapped them to the GH loop and the C-terminal region of VP1, respectively. Collectively, our findings provide a structural basis and important antigenic information for CVA6 VLP vaccine development.
Jinhuan Chen; Chao Zhang; Yu Zhou; Xiang Zhang; Chaoyun Shen; Xiaohua Ye; Wen Jiang; Zhong Huang; Yao Cong. A 3.0-Angstrom Resolution Cryo-Electron Microscopy Structure and Antigenic Sites of Coxsackievirus A6-Like Particles. Journal of Virology 2018, 92, e01257-17 .
AMA StyleJinhuan Chen, Chao Zhang, Yu Zhou, Xiang Zhang, Chaoyun Shen, Xiaohua Ye, Wen Jiang, Zhong Huang, Yao Cong. A 3.0-Angstrom Resolution Cryo-Electron Microscopy Structure and Antigenic Sites of Coxsackievirus A6-Like Particles. Journal of Virology. 2018; 92 (2):e01257-17.
Chicago/Turabian StyleJinhuan Chen; Chao Zhang; Yu Zhou; Xiang Zhang; Chaoyun Shen; Xiaohua Ye; Wen Jiang; Zhong Huang; Yao Cong. 2018. "A 3.0-Angstrom Resolution Cryo-Electron Microscopy Structure and Antigenic Sites of Coxsackievirus A6-Like Particles." Journal of Virology 92, no. 2: e01257-17.