Antibody therapies for the prevention and treatment of viral infections

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

The earliest application of antibodies as a treatment for viral infections can be traced back to the early 20th century, use of sera from infected humans who had recovered from the same infection. 1, 2 This crude treatment regimen, serum therapy, was gradually replaced by antibodies purified from pooled sera, intravenous immune globulin (IVIG). 3 Despite the success of both serum therapy and IVIG, no significant progress was made in the generation of antibodies as therapies until the hybridoma method was developed, enabling isolation of monoclonal antibodies (mAbs) from immunized mice in 1975. 4 Since the mid-1980s, several methods have been developed for the efficient isolation of mAbs against viruses from human and animal sources. One method involves using an antigen to pan antibody libraries constructed from immunoglobulin V H and V L variable regions genes of non-immune, vaccinated, or naturally infected individuals. In this method, antibody libraries are presented to antigens by display, for instance on phage, 5, 6 bacteria, 7 yeast, 8 or mammalian cells. 9 In other methods, antibodies are cloned from single-memory B cells [10] [11] [12] [13] or plasma B cells [14] [15] [16] isolated from vaccinated or naturally infected animals and human donors. mAbs have also been generated from immune sera using an approach that combines proteomics and reverse genetics. 17, 18 More recently, heavy and light chain paired mAbs have been generated by deep sequencing of the B-cell IgG repertoire. 19, 20 This review focuses on approaches to generate therapeutic mAbs to fight viral infection, examples of mAb therapies for viral infections, and the challenges of developing such therapies.