Antibody therapies for the prevention and treatment of viral infections

Salazar, Georgina; Zhang, Ningyan; Fu, Tong-Ming; An, Zhiqiang

broadly neutralizing antibodies have the potential to be developed into therapeutics against dengue infections. [142] [143] [144] [145] [146] [147] [148] Dengue targeting antibodies at high concentration may enhance infection. Therefore, therapeutic antibodies need to be engineered to abolish the interaction of antibodies to the FcγRs on macrophages, thus preventing ADE. 149 For example, a N297A mutation in the Fc region of D23-1G7C2 IgG1 was engineered to reduce the affinity of the IgG1 Fc region for FcγRs, resulting in a marked reduction in ADE activity in in vitro cell studies. 150 In another study, dengue neutralizing mAbs targeting distinct epitopes on the four DENV serotypes were engineered to prevent FcγR binding by introducing LALA (L234A-L235A) mutations in the IgG1 Fc region. The LALA variant did not enhance infection and neutralized DENV in vitro and in vivo as postexposure therapy in a mouse model of lethal DENV infection. 151 Perspective Only one mAb, specific to RSV, has been approved for prophylaxis use of viral infections. Several challenges impede the progress of the many antiviral mAbs in the pipeline. One key challenge is the relatively small market for antibody treatments of viral diseases, and potentially higher cost associated with production of recombinant antibodies, as compared to small molecule antivirals.