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Fusion of the molecular adjuvant C3d to cleavage-independent native-like HIV-1 Env trimers improves the elicited antibody response

Front Immunol. 2023-05; 
Shridhar Bale, Lifei Yang, Mehrdad Alirezaei, Richard Wilson, Takayuki Ota, Esmeralda D Doyle, Christopher A Cottrell, Javier Guenaga, Karen Tran, Wenjuan Li, Leonidas Stamatatos, David Nemazee, Andrew B Ward, Richard T Wyatt
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Proteins, Expression, Isolation and Analysis … B cells with or without PGV04 expression on their surface. … with the addition of PGV04 expression, indicating that C3d … for mammalian expression, synthesized (GenScript), and … Get A Quote

摘要

An effective HIV vaccine likely requires the elicitation of neutralizing antibodies (NAbs) against multiple HIV-1 clades. The recently developed cleavage-independent native flexibly linked (NFL) envelope (Env) trimers exhibit well-ordered conformation and elicit autologous tier 2 NAbs in multiple animal models. Here, we investigated whether the fusion of molecular adjuvant C3d to the Env trimers can improve B- cell germinal center (GC) formation and antibody responses. To generate Env-C3d trimers, we performed a glycine-serine- based (GS) flexible peptide linker screening and identified a linker range that allowed native folding. A 30-60- amino- acid- long linker facilitates Env-to-C3d association and achieves ... More

关键词

C3d, HIV-1, immunogenicity, molecular adjuvant, vaccine
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