Recombinant Human Anti-IgE Antibody Fab Fragment (47H4)

Brasiliensis–infected mice treated with M1′-specific antibody 47H4 wild-type or mIgG1 control antibody on day 21. Numbers indicate the percentage of CD19+ GFP+ cells and are representative of at least 3 experiments.

Brightbill, H. D., Jeet, S., Lin, Z., Yan, D., Zhou, M., Tan, M., ... & Wong, T. (2010). Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice. The Journal of clinical investigation, 120(6), 2218-2229.

(A) Experimental design for therapeutic M1′-specific antibody treatment of mouse allergic asthma model. Human M1′ knockin mice (n = 8 per group) were immunized with TNP-OVA/alum on day 0 and challenged with 7 daily aerosol administrations of TNP-OVA, starting on day 35. Mice were treated with 100 μg of M1′-specific antibody 47H4 or control mIgG1 antibody daily from day 39 through day. Treatment with M1′-specific antibody 47H4 antibody reduced (B) TNP-OVA-specific IgE levels, but did not affect (C) TNP-OVA–specific IgG1 levels. Treatment with M1′-specific antibody 47H4 antibody also reduced (D) the number of IgE-producing cells, but did not affect (E) the percentage of total syndecan+ plasma cells in the spleen, as measured on day. Results are mean ± SD. *P < 0.05 (Bonferroni correction for pairwise comparisons); **P < 0.05 (Dunnett's test).

Brightbill, H. D., Jeet, S., Lin, Z., Yan, D., Zhou, M., Tan, M., ... & Wong, T. (2010). Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice. The Journal of clinical investigation, 120(6), 2218-2229.

(A) The crystal structure of the humanized M1′-specific 47H4 antibody Fab (space filling mode; heavy chain is shown as blue, light chain is shown as gray) in complex with an M1′-derived
peptide (stick model, Ac-S6AQSQRAPDRVLCHSGQQQGLPRAAGGSVPHPRCH40-OOH) shows hydrogen bonds (dotted lines) between the h47H4 Fab and the M1′ peptide and burial of an arginine side chain from the M1′ peptide (Arg 11) in a central deep pocket in the h47H4 Fab. Numbers correspond to amino acid residues in the entire M1′ sequence. (B) The arginine binding pocket is formed by CDRs L1 (magenta), L3 (red), and H3 (purple), but CDR H2 (yellow) makes more contacts with the peptide than any other CDR. Amino acid side chains in the Fab that make important contacts with the peptide are shown as stick representations. (C) Four antibody aspartic acid residues in the Fab peptide-binding region combine to create a net negative electrostatic potential (red), which is complementary to the positive charges from M1′ peptide arginine side chains. H, heavy chain; L, light chain.

Brightbill, H. D., Jeet, S., Lin, Z., Yan, D., Zhou, M., Tan, M., ... & Wong, T. (2010). Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice. The Journal of clinical investigation, 120(6), 2218-2229.