Monoclonal antibodies for prophylactic and therapeutic use against viral infections

Abstract

Neutralizing antibodies play an essential part in antiviral immunity and are instrumental in preventing or modulating viral diseases. Polyclonal antibody preparations are increasingly being replaced by highly potent monoclonal antibodies (mAbs). Cocktails of mAbs and bispecific constructs can be used to simultaneously target multiple viral epitopes and to overcome issues of neutralization escape. Advances in antibody engineering have led to a large array of novel mAb formats, while deeper insight into the biology of several viruses and increasing knowledge of their neutralizing epitopes has extended the list of potential targets. In addition, progress in developing inexpensive production platforms will make antiviral mAbs more widely available and affordable.

Fig. 1

Antiviral mAb formats. A: Murine (left panel), humanized (middle) and fully human mAbs (right). The humanized mAb (e.g. palivizumab) contains both murine (blue) and human (yellow) sequences. B: Scheme of bispecific immunoadhesins. Immunoadhesins were generated using the Knob-into-hole technology which involves the introduction of certain ‘knob’ and ‘hole’ mutations in the CH3 domain of the Fc region to fuse two scFv-Fc molecules with different specificities. The mutated Fc regions favor HC heterodimerization over homodimerization, thereby minimizing the pairing of identical halves. C: Scheme of Morrison-type bispecific mAbs. Full-size mAbs and scFvs were fused to each other and issues of antibody stability were addressed by design optimization, including disulfide stabilization of scFvs and various linker designs. D: Scheme of multimeric mAb-fusion molecule. This transgenic plant-derived molecule combines the functional activities of the anti-HIV mAb b12 and the small microbicidal protein cyanovirin.