Therapeutics: Dengue virus envelope protein E (DENV_gp1)

In vitro and mouse studies suggest a mAb against DENV_gp1 could help treat infections by all four dengue serotypes. Antibodies elicited by previous infections with one dengue serotype can exacerbate subsequent infections with other dengue serotypes via an antibody-mediated enhanced viral uptake mechanism. Engineering of a previously identified mAb against all four dengue serotypes and in vitro screens for binding identified a lead mAb, VIS513, that bound domain III of dengue serotypes 1-4 with Kd values of 0.1-4.3 nM. In human monocyte cell lines, VIS513 decreased antibody-mediated enhanced viral uptake of serotypes 1-4 compared with a neutralizing mAb against the DENV_gp1 fusion loop. In mouse pups born to dams previously infected with dengue serotype 1, challenge with dengue serotype 2 followed by treatment with VIS513 increased survival and decreased clinical scores compared with treatment of pups with an unrelated isotype-matched mAb. Next steps include applying the structure-guided antibody engineering methods to target other infectious agents...