Human monoclonal antibodies for prophylaxis and therapy of viral infections

Abstract

Monoclonal antibody (mAb) technology has reached a state of maturity making it possible to rapidly discover and produce fully human mAbs which neutralize any given virus in vitro. Several antibodies have also shown good prophylactic and therapeutic efficacy in relevant animal models of viral disease. Surprisingly, only one antiviral mAb has been licensed to date; it is used to prevent infection with respiratory syncytial virus in at-risk infants. Certain paradigms of mAbs prevailing in industry and academia are obstacles to the development of further antiviral antibodies for clinical use. There is a perception that mAbs are much more effective in prophylactic than therapeutic use, offer limited breadth of protection against different viral strains, are prone to select neutralization escape variants and need to be given in high doses, which are still comparatively costly to manufacture. Based on a review of the literature and our own data, we propose that by combining two or more non- competing neutralizing antibodies, viral escape can effectively be controlled and in case of synergistic action of the mAbs it may be possible to significantly reduce the total antibody concentration required for protection. The combination of mAbs with specific antiviral drugs has the potential to expand their use from pre- and post-exposure prophylaxis to therapy of acute and chronic viral infections.