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Exploration of broadly neutralizing antibody fragments produced in bacteria for the control of HIV.
- Source :
-
Human vaccines & immunotherapeutics [Hum Vaccin Immunother] 2017 Nov 02; Vol. 13 (11), pp. 2726-2737. Date of Electronic Publication: 2017 Sep 26. - Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- Antibodies, Neutralizing administration & dosage
Antibodies, Neutralizing biosynthesis
Escherichia coli genetics
Escherichia coli immunology
HIV Antibodies administration & dosage
HIV Antibodies biosynthesis
HIV Antibodies chemistry
HIV Infections immunology
HIV Infections prevention & control
HIV Infections virology
HIV-1 immunology
Humans
Neutralization Tests
Proof of Concept Study
Single-Chain Antibodies biosynthesis
Antibodies, Neutralizing therapeutic use
Bacteria immunology
HIV Antibodies therapeutic use
HIV Infections therapy
Single-Chain Antibodies immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2164-554X
- Volume :
- 13
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Human vaccines & immunotherapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 28949787
- Full Text :
- https://doi.org/10.1080/21645515.2017.1368935