A broad-spectrum and highly potent human monoclonal antibody cocktail for rabies prophylaxis

Abstract

Post-exposure prophylaxis (PEP) is highly effective in preventing disease progression of rabies when used in timely and appropriate manner. The key treatment for PEP is infiltration of rabies immune globulin (RIG) into lesion site after bite exposure, besides wound care and vaccination. Unfortunately, however, RIG is expensive and its supply is limited. Currently, several anti-rabies virus monoclonal antibody (mAb) products are under development as alternatives to RIG, and two recently received regulatory approval in India. In this study, fully human mAbs that recognize different rabies virus glycoprotein conformational antigenic site (II and III) were created from peripheral blood mononuclear cells of heathy vaccinated subjects. These mAbs neutralized a diverse range of lyssavirus types. As at least two anti-rabies virus mAbs are recommended for use in human PEP to ensure broad coverage against diverse lyssaviruses and to minimize possible escape variants, two most potent mAbs, NP-19-9 and 11B6, were selected to be used as cocktail treatment. These two mAbs were broadly reactive to different types of lyssaviruses isolates, and were shown to have no interference with each other. These results suggest that NP-19-9 and 11B6 are potent candidates to be used for PEP, suggesting further studies involving clinical studies in human.

Antiviral mechanisms of two broad-spectrum monoclonal antibodies for rabies prophylaxis and therapy

“…Over the years, the scientific community has attempted to develop several anti-rabies virus (RABV) monoclonal antibodies (mAbs) as alternatives to RIGs ( 3 , 4 ), with three products so far available in the Indian or Chines market, namely, Rabishield (containing a unique human [h] mAb, 17C7-RAB1) ( 5 ), Twinrab (containing a cocktail of two murine mAbs, M777-16-3 and 62-71-3) ( 6 ), and Xunke (composed of a unique hmAb, ormutivimab) ( 7 , 8 ). Additional products may become commercially available in the next future, such as CL184 (a cocktail of two human mAbs, CR57, and CR4098) ( 9 ), SYN023 (a cocktail of two humanized mAbs, called CTB011 and CTB012) ( 10 ), the cocktail of human mAbs 11B6 + NP-19-9 ( 11 ), and a combination of three human mAbs (CR57, RV08, and RV3A5) ( 12 ). In spite of preliminary evidence showing that mAbs might clear RABV from infected animals ( 13 ), no effective therapy for symptomatic rabies has been developed to date.…”