Recombinant Human Antibody (C05) is capable of binding to H3N2 HA, expressed in HEK 293 cells. Expressed as the combination of a heavy chain (HC) containing VH from anti-H3N2 HA mAb and CH1-3 region of human IgG and a light chain (LC) encoding VL from anti-H3N2 HA proteins mAb and CL of human kappa light chain. Exists as a disulfide linked dimer of the HC and LC hetero-dimer under non-reducing condition. C5 recognizes conserved elements of the receptor binding site on the hemagglutinin (HA) surface glycoprotein.
Figure 1 Impact of L194P substitution on antigenicity.
(B-C) Biolayer interferometry (BLI) was used to measure the binding kinetics of C05 IgG against the recombinant HA proteins of (B) Bris07 P194 and (C) Bris07 L194. (D) HAI assay of C05 IgG against Bris07 P194 and Bris07 L194 viruses. Duplicates were performed for each of Bris07 P194 and L194.
Wu, N. C., Zost, S. J., Thompson, A. J., Oyen, D., Nycholat, C. M., McBride, R., ... & Wilson, I. A. (2017). A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine. PLoS pathogens, 13(10), e1006682.
Figure 2 C05 protects mice from lethal virus challenge.
a, b, Survival and weight loss were monitored in response to varying amounts of C05 IgG administered prophylactically to mice 24 h before challenge with 25 × the 50% mouse lethal dose (MLD₅₀) of A/Memphis/3/2008 (H1N1) (a) or 333 MLD₅₀ of A/X-31/1968 (H3N2) viruses (b). c, d, A single therapeutic dose of 15 mg/kg C05 IgG was delivered 1, 2, 3, 4 or 5 days post-infection (DPI) with 25 × MLD₅₀ of A/Memphis/3/2008 (c) or 33 × MLD₅₀ of A/X-31/1968 viruses (d). n = 5 mice for all studies. Error bars denote ± s.d.
Ekiert, D. C., Kashyap, A. K., Steel, J., Rubrum, A., Bhabha, G., Khayat, R., … Wilson, I. A. (2012). Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature, 489(7417), 526–532.
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• Increased sensitivity
• Confirmed specificity
• High repeatability
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