From Whole Monoclonal Antibodies to Single Domain Antibodies: Think Small

2012 ◽  
pp. 3-13 ◽  
Author(s):  
Jean-Luc Teillaud
Antibodies ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 14 ◽  
Author(s):  
Walter Ramage ◽  
Tiziano Gaiotto ◽  
Christina Ball ◽  
Paul Risley ◽  
George W. Carnell ◽  
...  

Influenza B virus (IBV) circulates in the human population and causes considerable disease burden worldwide, each year. Current IBV vaccines can struggle to mount an effective cross-reactive immune response, as strains become mismatched, due to constant antigenic changes. Additional strategies which use monoclonal antibodies, with broad reactivity, are of considerable interest, both, as diagnostics and as immunotherapeutics. Alternatives to conventional monoclonal antibodies, such as single domain antibodies (NanobodiesTM) with well-documented advantages for applications in infectious disease, have been emerging. In this study we have isolated single domain antibodies (sdAbs), specific to IBV, using alpacas immunised with recombinant hemagglutinin (HA) from two representative viruses, B/Florida/04/2006 (B/Yamagata lineage) and B/Brisbane/60/2008 (B/Victoria lineage). Using phage display, we have isolated a panel of single domain antibodies (sdAbs), with both cross-reactive and lineage-specific binding. Several sdAbs recognise whole virus antigens, corresponding to influenza B strains included in vaccines spanning over 20 years, and were capable of neutralising IBV pseudotypes corresponding to prototype strains from both lineages. Lineage-specific sdAbs recognised the head domain, whereas, sdAbs identified as cross-reactive could be classified as either head binding or stem binding. Using yeast display, we were able to correlate lineage specificity with naturally occurring sequence divergence, at residue 122 in the highly variable 120 loop of the HA1 domain. The single domain antibodies described, might have applications in IBV diagnostics, vaccine potency testing and as immunotherapeutics.


2010 ◽  
Author(s):  
Ellen Goldman ◽  
Andrew Hayhurst

Author(s):  
Carla F.C. Fernandes ◽  
Soraya S. Pereira ◽  
Marcos B. Luiz ◽  
Nauanny K.R.L. Silva ◽  
Marcela Cristina da Silva ◽  
...  

Science ◽  
2021 ◽  
Vol 371 (6530) ◽  
pp. 681-682 ◽  
Author(s):  
Xavier Saelens ◽  
Bert Schepens

Author(s):  
Nicola Wanner ◽  
Thomas Eden ◽  
Nastassia Liaukouskaya ◽  
Friedrich Koch-Nolte

AbstractCurrent therapeutic options for renal diseases are limited, and the search for disease-specific treatments is ongoing. Nanobodies, single-domain antibodies with many advantages over conventional antibodies, provide flexible, easy-to-format biologicals with many possible applications. Here, we discuss the potential use of nanobodies for renal diseases.


Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 927
Author(s):  
Sebas D. Pronk ◽  
Erik Schooten ◽  
Jurgen Heinen ◽  
Esra Helfrich ◽  
Sabrina Oliveira ◽  
...  

Antibody-drug conjugates (ADCs) are currently used for the targeted delivery of drugs to diseased cells, but intracellular drug delivery and therefore efficacy may be suboptimal because of the large size, slow internalization and ineffective intracellular trafficking of the antibody. Using a phage display method selecting internalizing phages only, we developed internalizing single domain antibodies (sdAbs) with high binding affinity to rat PDGFRβ, a receptor involved in different types of diseases. We demonstrate that these constructs have different characteristics with respect to internalization rates but all traffic to lysosomes. To compare their efficacy in targeted drug delivery, we conjugated the sdAbs to a cytotoxic drug. The conjugates showed improved cytotoxicity correlating to their internalization speed. The efficacy of the conjugates was inhibited in the presence of vacuolin-1, an inhibitor of lysosomal maturation, suggesting lysosomal trafficking is needed for efficient drug release. In conclusion, sdAb constructs with different internalization rates can be designed against the same target, and sdAbs with a high internalization rate induce more cell killing than sdAbs with a lower internalization rate in vitro. Even though the overall efficacy should also be tested in vivo, sdAbs are particularly interesting formats to be explored to obtain different internalization rates.


2011 ◽  
Vol 173 (2) ◽  
pp. 300-305 ◽  
Author(s):  
Bert Thys ◽  
Dirk Saerens ◽  
Lise Schotte ◽  
Gerrit De Bleeser ◽  
Serge Muyldermans ◽  
...  

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