Recombinant Mouse Antibody (E106) is capable of binding to DENV-1 Envelope protein DIII, expressed in Chinese Hamster Ovary cells (CHO).
Figure 1 Binding of MAbs to cells infected with different genotypes of DENV-1.
C6/36 insect cells were infected with strains of DENV-1 virus corresponding to all five genotypes. After fixation and permeabilization, MAbs were incubated with infected cells and binding was assessed by flow cytometry. The data shown are representative histograms from two independent experiments with a neutralizing (DENV1-E106, upper panels) MAb.
Shrestha, B., Brien, J. D., Sukupolvi-Petty, S., Austin, S. K., Edeling, M. A., Kim, T.,... & Diamond, M. S. (2010). The development of therapeutic antibodies that neutralize homologous and heterologous genotypes of dengue virus type 1. PLoS pathogens, 6(4), e1000823.
Figure 2 Dose response of protective efficacy MAbs in mice infected with DENV-1.
AG129 mice were passively transferred saline or 20, 100, or 500 µg of (A) DENV1-E99, (B) DENV1-E103, (C) DENV1-E105, and (D) DENV1-E106 MAbs one day before infection with 106 PFU of West Pac-74 (genotype 4) by an IP route. Mice were monitored for survival for 60 days after infection. The survival curves were constructed from data of two independent experiments. The number of animals for each antibody dose ranged from 5 to 10 per group.
Shrestha, B., Brien, J. D., Sukupolvi-Petty, S., Austin, S. K., Edeling, M. A., Kim, T.,... & Diamond, M. S. (2010). The development of therapeutic antibodies that neutralize homologous and heterologous genotypes of dengue virus type 1. PLoS pathogens, 6(4), e1000823.
Figure 3 Therapeutic efficacy of strongly neutralizing antibodies in mice after DENV-1 infection.
Mice were administered saline or a single 500 µg dose of DENV1-E105 or DENV1-E106 MAbs at day (A) 2 or (B) 4 after infection with 106 PFU of West Pac-74 (genotype 4) by an IP route. Mice were monitored for survival for 60 days after infection. The number of animals for each antibody ranged from 10 to 11 per group.
Shrestha, B., Brien, J. D., Sukupolvi-Petty, S., Austin, S. K., Edeling, M. A., Kim, T.,... & Diamond, M. S. (2010). The development of therapeutic antibodies that neutralize homologous and heterologous genotypes of dengue virus type 1. PLoS pathogens, 6(4), e1000823.
Figure 4 Qualitative ELISA binding of MAbs and Fabs to DENV-1.
E106 MAb binds virions to a similar extent as E103 MAb but E106 Fab binding is significantly less than E103 Fab (P<0.0001). The negative control is E16. The results are from two ELISA experiments performed in duplicate and without background subtraction. The limit of detection was determined by performing the assay in the absence of virus.
Shrestha, B., Brien, J. D., Sukupolvi-Petty, S., Austin, S. K., Edeling, M. A., Kim, T.,... & Diamond, M. S. (2010). The development of therapeutic antibodies that neutralize homologous and heterologous genotypes of dengue virus type 1. PLoS pathogens, 6(4), e1000823.
Figure 5 Time and temperature dependence of neutralization.
Shrestha, B., Brien, J. D., Sukupolvi-Petty, S., Austin, S. K., Edeling, M. A., Kim, T.,... & Diamond, M. S. (2010). The development of therapeutic antibodies that neutralize homologous and heterologous genotypes of dengue virus type 1. PLoS pathogens, 6(4), e1000823.
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