Identification of Human Norovirus GII.3 Blockade Antibody Epitopes

Yi, Yufang; Wang, Shuxia; Wang, Xiaoli; Xiong, Pei; Li, Renjie; Zhang, Chao; Yin, Feifei; Huang, Zhong

doi:10.3390/v13102058

Cited by 3 publications

(2 citation statements)

References 58 publications

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“…Antibody sequence analysis was performed using IgBLAST [ 42 ]. MAbs were purified using protein G agarose resin 4FF (Yeasen, China) according to our previously described protocol [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

Mapping cross-variant neutralizing sites on the SARS-CoV-2 spike protein

Wang

Zhang

et al. 2022

Emerging Microbes & Infections

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The emergence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of currently approved vaccines and authorized therapeutic monoclonal antibodies (MAbs). It is hence important to continue searching for SARS-CoV-2 broadly neutralizing MAbs and defining their epitopes. Here, we isolate 9 neutralizing mouse MAbs raised against the spike protein of a SARS-CoV-2 prototype strain and evaluate their neutralizing potency towards a panel of variants, including B.1.1.7, B.1.351, B.1.617.1, and B.1.617.2. By using a combination of biochemical, virological, and cryo-EM structural analyses, we identify three types of cross-variant neutralizing MAbs, represented by S5D2, S5G2, and S3H3, respectively, and further define their epitopes. S5D2 binds the top lateral edge of the receptor-binding motif within the receptor-binding domain (RBD) with a binding footprint centred around the loop 477–489 , and efficiently neutralizes all variant pseudoviruses, but the potency against B.1.617.2 was observed to decrease significantly. S5G2 targets the highly conserved RBD core region and exhibits comparable neutralization towards the variant panel. S3H3 binds a previously unreported epitope located within the evolutionarily stable SD1 region and is able to near equally neutralize all of the variants tested. Our work thus defines three distinct cross-variant neutralizing sites on the SARS-CoV-2 spike protein, providing guidance for design and development of broadly effective vaccines and MAb-based therapies.

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“…Antibody sequence analysis was performed using IgBLAST [ 42 ]. MAbs were purified using protein G agarose resin 4FF (Yeasen, China) according to our previously described protocol [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

Mapping cross-variant neutralizing sites on the SARS-CoV-2 spike protein

Wang

Zhang

et al. 2022

Emerging Microbes & Infections

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“…MAbs were purified from ascites using protein G agarose resin 4FF (Yeasen, China) according to our previously described protocol 46 . Fabs were obtained by papain digestion of anti-CVA16 MAbs and then purified using Protein G column and Sephacryl S-100 column (GE Healthcare, USA) according to our previously described protocols 47 .…”

Section: Preparation and Sequencing Of Mabs And Fabsmentioning

confidence: 99%

Molecular mechanism of antibody neutralization of coxsackievirus A16

Zhang,

Liu,

Shi

et al. 2022

Nat Commun

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Coxsackievirus A16 (CVA16) causes hand, foot and mouth disease in infants and young children. However, no vaccine or anti-viral agent is currently available for CVA16. Here, the functions and working mechanisms of two CVA16-specific neutralizing monoclonal antibodies (MAbs), 9B5 and 8C4, are comprehensively investigated. Both 9B5 and 8C4 display potent neutralization in vitro and prophylactic and therapeutic efficacy in a mouse model of CVA16 infection. Mechanistically, 9B5 exerts neutralization primarily through inhibiting CVA16 attachment to cell surface via blockade of CVA16 binding to its attachment receptor, heparan sulfate, whereas 8C4 functions mainly at the post-attachment stage of CVA16 entry by interfering with the interaction between CVA16 and its uncoating receptor SCARB2. Cryo-EM studies show that 9B5 and 8C4 target distinct epitopes located at the 5-fold and 3-fold protrusions of CVA16 capsids, respectively, and exhibit differential binding preference to three forms of naturally occurring CVA16 particles. Moreover, 9B5 and 8C4 are compatible in formulating an antibody cocktail which displays the ability to prevent virus escape seen with individual MAbs. Together, our work elucidates the functional and structural basis of CVA16 antibody-mediated neutralization and protection, providing important information for design and development of effective CVA16 vaccines and antibody therapies.

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Genetic characterization of rarely reported GII.3[P25] norovirus strain detected in patients with acute gastroenteritis in Huzhou, China, 2021

Zhang

Li³

et al. 2023

Virologica Sinica

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Identification of Human Norovirus GII.3 Blockade Antibody Epitopes

Cited by 3 publications

References 58 publications

Mapping cross-variant neutralizing sites on the SARS-CoV-2 spike protein

Mapping cross-variant neutralizing sites on the SARS-CoV-2 spike protein

Molecular mechanism of antibody neutralization of coxsackievirus A16

Genetic characterization of rarely reported GII.3[P25] norovirus strain detected in patients with acute gastroenteritis in Huzhou, China, 2021

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