Isolation of anin VitroAffinity-Matured, Thermostable “Headless” HA Stem Fragment That Binds Broadly Neutralizing Antibodies with High Affinity

Biochemistry ◽  
2018 ◽  
Vol 57 (26) ◽  
pp. 3817-3829 ◽  
Author(s):  
Tariq Ahmad Najar ◽  
Uddipan Kar ◽  
Jessica A. Flynn ◽  
Raghavan Varadarajan
Keyword(s):  
Neutralizing Antibodies ◽  
Broadly Neutralizing Antibodies ◽  
High Affinity ◽  
Stem Fragment

scholarly journals Structure of the apo anti-influenza CH65 Fab

2015 ◽  
Vol 71 (2) ◽  
pp. 145-148 ◽  
Author(s):  
Peter S. Lee ◽  
Ashley J. Arnell ◽  
Ian A. Wilson
Keyword(s):  
Neutralizing Antibodies ◽  
Affinity Maturation ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Human Antibody ◽  
Broadly Neutralizing Antibodies ◽  
High Affinity ◽  
Influenza Hemagglutinin ◽  
Universal Influenza Vaccine ◽  
Complementarity Determining Region

Influenza viruses remain a persistent challenge to human health owing to their inherent ability to evade the immune response by antigenic drift. However, the discovery of broadly neutralizing antibodies (bnAbs) against divergent viruses has sparked renewed interest in a universal influenza vaccine and novel therapeutic opportunities. Here, a crystal structure at 1.70 Å resolution is presented of the Fab of the human antibody CH65, which has broad neutralizing activity against a range of seasonal H1 isolates. Previous studies proposed that affinity maturation of this antibody lineage pre-organizes the complementarity-determining region (CDR) loops into an energetically favorable HA-bound conformation. Indeed, from the structural comparisons of free and HA-bound CH65 presented here, the CDR loops, and in particular the heavy-chain CDR3, adopt the same conformations in the free and bound forms. Thus, these findings support the notion that affinity maturation of the CH65 lineage favorably preconfigures the CDR loops for high-affinity binding to influenza hemagglutinin.

scholarly journals Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies

2019 ◽  
Vol 15 (9) ◽  
pp. e1008026 ◽  
Author(s):  
Celia C. LaBranche ◽  
Rory Henderson ◽  
Allen Hsu ◽  
Shay Behrens ◽  
Xuejun Chen ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Common Ancestor ◽  
Broadly Neutralizing Antibodies ◽  
High Affinity ◽  
Hiv 1

scholarly journals Camel nanobodies broadly neutralize SARS-CoV-2 variants

2021 ◽  
Author(s):  
Jessica Hong ◽  
Hyung Joon Kwon ◽  
Raul Cachau ◽  
Catherine Z Chen ◽  
Kevin John Butay ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Conformational State ◽  
Complex Structures ◽  
Receptor Binding Domain ◽  
Broadly Neutralizing Antibodies ◽  
Dromedary Camels ◽  
Lethal Challenge ◽  
High Affinity

With the emergence of SARS-CoV-2 variants, there is urgent need to develop broadly neutralizing antibodies. Here, we isolate two VHH nanobodies (7A3 and 8A2) from dromedary camels by phage display, which have high affinity for the receptor-binding domain (RBD) and broad neutralization activities against SARS-CoV-2 and its emerging variants. Cryo-EM complex structures reveal that 8A2 binds the RBD in its up mode and 7A3 inhibits receptor binding by uniquely targeting a highly conserved and deeply buried site in the spike regardless of the RBD conformational state. 7A3 at a dose of ≥5 mg/kg efficiently protects K18-hACE2 transgenic mice from the lethal challenge of B.1.351 or B.1.617.2, suggesting that the nanobody has promising therapeutic potentials to curb the COVID-19 surge with emerging SARS-CoV-2 variants.

Broadly Neutralizing Antibodies (BNAbs): templates for HIV-1 vaccine design

2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Lixin Yan ◽  
◽  
Lihong Liu ◽  
Yilin Wang ◽  
Xi Huang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Design ◽  
Broadly Neutralizing Antibodies ◽  
Hiv 1
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