Exploration of broadly neutralizing antibody fragments produced in bacteria for the control of HIV

While broadly neutralizing antibodies (bnAbs) are a promising preventative and therapeutic tool for HIV infection, production is difficult and expensive. Production of antibody-like fragments in bacterial cytoplasm provides a cheaper alternative. This work explored the transplantation of the complem...

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Bibliographic Details
Main Authors: Sarah B. Lloyd (Author), Keith P. Niven (Author), Ben R. Kiefel (Author), David C. Montefiori (Author), Arnold Reynaldi (Author), Miles P. Davenport (Author), Stephen J. Kent (Author), Wendy R. Winnall (Author)
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Published: Taylor & Francis Group, 2017-11-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Sarah B. Lloyd  |e author 
700 1 0 |a Keith P. Niven  |e author 
700 1 0 |a Ben R. Kiefel  |e author 
700 1 0 |a David C. Montefiori  |e author 
700 1 0 |a Arnold Reynaldi  |e author 
700 1 0 |a Miles P. Davenport  |e author 
700 1 0 |a Stephen J. Kent  |e author 
700 1 0 |a Wendy R. Winnall  |e author 
245 0 0 |a Exploration of broadly neutralizing antibody fragments produced in bacteria for the control of HIV 
260 |b Taylor & Francis Group,   |c 2017-11-01T00:00:00Z. 
500 |a 2164-5515 
500 |a 2164-554X 
500 |a 10.1080/21645515.2017.1368935 
520 |a While broadly neutralizing antibodies (bnAbs) are a promising preventative and therapeutic tool for HIV infection, production is difficult and expensive. Production of antibody-like fragments in bacterial cytoplasm provides a cheaper alternative. This work explored the transplantation of the complementarity determining regions of the anti-HIV bnAbs PGT121 and 10E8 onto a single-chain variable fragment (scFv) scaffold, previously discovered through a novel screening platform. The scaffolded 10E8 scFv, but not the scaffolded PGT121 scFv, was soluble in bacterial cytoplasm, enabling efficient production in bacteria. Three additional multimeric constructs employing the scaffolded 10E8 scFv were also generated and soluble versions produced in bacteria. However, the constructs were found to have substantially lost anti-HIV binding function and had completely abrogated neutralizing activity. Overall, while this study provides a proof-of-concept for anti-HIV bnAb construct production in bacterial cytoplasm, future refinement of these technologies will be required to realize the goal of producing inexpensive and effective bnAb-like tools for the control of HIV. 
546 |a EN 
690 |a 10e8 
690 |a broadly neutralizing antibodies 
690 |a diabodies 
690 |a e. coli expression 
690 |a human immunodeficiency virus 
690 |a pgt121 
690 |a single-chain variable fragment antibodies 
690 |a tandem-scfv 
690 |a Immunologic diseases. Allergy 
690 |a RC581-607 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Human Vaccines & Immunotherapeutics, Vol 13, Iss 11, Pp 2726-2737 (2017) 
787 0 |n http://dx.doi.org/10.1080/21645515.2017.1368935 
787 0 |n https://doaj.org/toc/2164-5515 
787 0 |n https://doaj.org/toc/2164-554X 
856 4 1 |u https://doaj.org/article/89a2356a613b4dbc9539b96d6c42d890  |z Connect to this object online.