Antibody therapies for the prevention and treatment of viral infections

Abstract

Antibodies are an important component in host immune responses to viral pathogens. Because of their unique maturation process, antibodies can evolve to be highly specific to viral antigens. Physicians and researchers have been relying on such high specificity in their quest to understand host-viral interaction and viral pathogenesis mechanisms and to find potential cures for viral infection and disease. With more than 60 recombinant monoclonal antibodies developed for human use in the last 20 years, monoclonal antibodies are now considered a viable therapeutic modality for infectious disease targets, including newly emerging viral pathogens such as Ebola representing heightened public health concerns, as well as pathogens that have long been known, such as human cytomegalovirus. Here, we summarize some recent advances in identification and characterization of monoclonal antibodies suitable as drug candidates for clinical evaluation, and review some promising candidates in the development pipeline.

Fig. 1

Schematic representation of generation of mAbs using phage display. This method has the advantage of being relatively easy with the potential to generate VH and VL combinations not found in nature. The diagram was generated based on a combination of publications^,

Fig. 2

Schematic of isolation of mAbs from memory B cells. When these cells producing antibodies with desired characteristics can be found, a supply of these antibodies can be maintained by culture and cloning, immortalization, or direct cloning. The diagram was generated by summarizing multiple published papers. The diagram was generated based on a combination of publications^{–, –}

Fig. 3

Overview of isolation, culture, and antibody gene cloning from plasma B cells. This method can be an efficient way of generating antibodies with desired specificity given the right antigen bait and timing. The diagram was generated based on a combination of publications^{, , –}

Fig. 4

Representation of the combination of proteomics and high-throughput sequencing approaches to isolation of relevant mAbs from human donors. Analysis of nucleic acids from B cells combined with proteomic analysis of antibodies in serum provides a deeper understanding of the humoral response to viral infection and vaccinations. The diagram was generated based on a combination of publications^{, , ,}