Bactericidal action of a complement-independent antibody against relapsing fever Borrelia resides in its variable region

The Journal of Immunology : Official Journal of the American Association of Immunologists
Timothy J LaRoccaJ L Benach

Abstract

A single chain variable fragment (scFv) of CB515, a complement-independent bactericidal monoclonal IgM against a relapsing fever Borrelia, was constructed to investigate the region wherein the unique bactericidal function resides. Monomeric CB515 scFv (26 kDa) was capable of binding its Ag on whole organisms and by immunoblot. This binding was shown to be species and serotype-specific to the 19 kDa variable small protein, recognized by its parent monoclonal IgM. A dose-dependent bactericidal effect of the CB515 scFv was detected by direct enumeration of spirochetes. Spirochetes incubated with the CB515 scFv before inoculation into mice grew into escape mutants, whereas spirochetes incubated with an irrelevant scFv developed as the original infecting serotype. This bactericidal effect, as seen at the ultrastructural level, was due to disruption of the outer membrane and to severe membrane blebbing eventually progressing to lysis. These results indicate that the variable region of CB515 is responsible for this bactericidal activity and that the constant region of the Ab is dispensable.

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Citations

Jun 25, 2009·Proceedings of the National Academy of Sciences of the United States of America·Timothy J LaRoccaJorge L Benach
Mar 2, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xuemei XieJ Christopher Hall
Dec 20, 2011·Nature Immunology·Arturo Casadevall, Liise-Anne Pirofski
Apr 15, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alex WagemakersJoppe W Hovius
Dec 26, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Susan MalkielJorge L Benach
Feb 6, 2020·Antimicrobial Agents and Chemotherapy·Gabrielle RichardGreg Hussack
Apr 11, 2020·Trends in Immunology·Jordan D Dimitrov, Sébastien Lacroix-Desmazes
May 14, 2010·Journal of Clinical Microbiology·A ToledoJ L Benach
Jul 6, 2021·Clinical & Translational Immunology·Behnoush SoltanmohammadiFatemeh Rahimi-Jamnani

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