Antibody therapies for the prevention and treatment of viral infections

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

As discussed above, Fc region engineering has been shown effective for increasing the half-life of therapeutic antibodies, for instance the RSV mAb motavizumab YTE, and for preventing ADE through reduced FcR binding, as for dengue antibodies. The interactions of the Fc domain with diverse other receptors provides additional opportunities for engineering to optimize therapeutic efficacy of antibodies. The advantages and disadvantages of engineering approaches was recently reviewed by Bournazos and Ravetch. 155 Passive transfer of antibodies for the prevention and treatment of viral infections is easy to manage, but the high cost associated with antibody therapies is prohibitive in prophylactic use of antibodies for intractable viruses such as HIV and influenza A virus for a large population, particularly in low-resource areas. 156 One alternative to passive administration of antibody therapies involves the delivery of transgenes encoding well characterized neutralizing antibodies by a vector. The transgenes direct the expression of antibodies in non-hematopoietic cells, which then secrete mAbs into circulation. It has been demonstrated that intramuscular delivery by electroporation of synthetic DNA plasmids engineered to express modified human mAbs against multiple DENV serotypes confers protection against DENV disease and prevents ADE of disease in mice. 157 More work is needed before clinical applications, but vector delivery of prophylactic or therapeutic antibodies against viral infections is a promising alternative to the current practice of passive transfer.