Biochemical features and antiviral activity of a monomeric catalytic antibody light‐chain 23D4 against influenza A virus

Abstract

Catalytic antibodies have exhibited interesting functions against some infectious viruses such as HIV, rabies virus, and influenza virus in vitro as well as in vivo. In some cases, a catalytic antibody light chain takes on several structures from the standpoint of molecular size (monomer, dimer, etc.) and/or isoelectronic point. In this study, we prepared a monomeric 23D4 light chain by mutating the C-terminal Cys to Ala of the wild-type. The mutated 23D4 molecule took a simple monomeric form, which could hydrolyze synthetic 4-methyl-coumaryl-7-amide substrates and a plasmid DNA. Because the monomeric 23D4 light chain suppressed the infection of influenza virus A/Hiroshima/37/2001 in an in vitro assay, the corresponding experiments were conducted in vivo, after the virus strain (which was taken from a human patient) was successfully adapted into BALB/cN Sea mice. In the experiments, a mixture of the monomeric 23D4 and the virus was nasally administered 1) with preincubation and 2) without preincubation. As a result, the monomeric 23D4 clearly exhibited the ability to suppress the influenza virus infection in both cases, indicating a potential drug for preventing infection of the influenza A virus.-Hifumi, E., Arakawa, M., Matsumoto, S., Yamamoto, T., Katayama, Y., Uda, T. Biochemical features and antiviral activity of a monomeric catalytic antibody light-chain 23D4 against influenza A virus. FASEB J. 29, 2347-2358 (2015). www.fasebj.org

Structural Diversity Problems and the Solving Method for Antibody Light Chains

“…The proteins were expressed in Escherichia coli in accordance with the protocol described in the section of Materials and Methods in Refs. [19,31,32]. Methionine was adducted at the N-terminus and confirmed by amino acid sequence analysis after cloning the cDNA of the light chain into the Nco I site of the pET-20b vector.…”

“…With respect to catalytic antibodies, they have extensively been developed [4][5][6][7][8][9][10][11][12][13][14] for the last two decades from the viewpoint of both basic research and the application, where it has been proved that there are many catalytic antibodies being effective against anti-rabies virus [15], anti-influenza virus [16], anti-Helicobacter pylori [17], anti-HIV [7,8,10], anti-Alzheimer's disease [14,18], etc. Interestingly, some of them have been advanced to the stage tested in vivo in this decade [15][16][17][18][19]. In the case of catalytic antibodies, some of them play the role as a whole structure of IgG [5,9,11,13], IgA [20], or IgM [21][22][23].…”

Antibody-Mediated Catalysis in Infection and Immunity

“…The 18B7 MAb was studied in a phase I clinical trial for the treatment of C. neoformans infection, although its catalytic activity was not known at the time (65). Catalytic antibodies targeting influenza virus (34,67), rabies virus (53), and HIV (68) are currently in early development but show potential for future applications. Another catalytic antibody generated using a synthetic randomized peptide library was found to hydrolyze Her2 mRNA in breast cancer cells, indicating a potential therapeutic role in gene silencing (32).…”

Catalytic antibodies in patients with systemic lupus erythematosus

“…Thus, this natural clearance of immune complexes can lower the deleterious secondary effects such as inflammation and infiltration of various molecules of the immune system. Catalytic antibodies are described both in physiology as well as under various pathological conditions, such as asthma, hemophilia A, multiple sclerosis, rheumatoid arthritis, Hashimoto's thyroiditis, sepsis, graft versus host disease in transplantation, and others (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Depending on the target antigen, both pathogenic and beneficial role of catalytic antibodies have been described (10,19).…”