Antibody therapies for the prevention and treatment of viral infections

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

Another key challenge is the competition of other forms of treatment and prevention. Vaccines are often still the best approach to control viral infections, often with benefits of lifelong immunity. Even after effective mAb therapies are developed, their widespread application may be impractical due to the high costs of conventional production compared to other countermeasures against disease from viral infections. One way to address the problem of the high cost of mAb therapies is to reduce the cost of production. For instance, production of mAbs in scFv or Fab form or as camelid nanobodies enables relatively inexpensive expression in prokaryotic systems. 152 Another way to address the problem of high costs is financing through partnerships with traditional donors and newer funding sources such as the Gates Foundation. For example, development impact bonds have been tested as a way to eliminate rabies infection in dogs, in turn reducing demand for expensive treatments for humans. 153 A third key challenge is the complexity of pathology, epidemiology, and immunology that can be associated with infection. The way kinetics of infection informs therapeutic strategy, for instance, explains why no dengue mAbs are in clinical trials and why vaccination is the preferred method to control influenza. For dengue and influenza A, symptoms often appear after the peak of viremia; 139, 154 an antibody applied for passive immunotherapy would have to be used before the onset of symptoms to be early enough to avoid viremia. One potential solution is matching a therapeutic antibody with a rapid, point of care diagnostic test. The diagnostic could be used to identify patients with infection and susceptibility to severe disease who would benefit from passive immunotherapy with the therapeutic antibody. Finally, viruses can have complexity that prevents development of a single lasting treatment, for instance multiple strains, rapid evolution, and obscure mechanisms of infection and neutralization escape.