[Development of Recombinant Human Monoclonal Antibody Cocktail for Post-exposure Rabies Prophylaxis]

To evaluate the neutralizing potency and spectrum of three recombinant human mAbs CR57(Ⅰ), RV08(Ⅱ), RV3A5 (Ⅲ) and the triple combination cocktail against antigenic site I, II and III on rabies virus glycoprotein, a standard fluorescent antibody virus neutralization test(FAVN)on several RV vaccine strains, fixed strains, and street strains of total 11 trains was performed by incubation of RV with varying concentrations of antibody followed by incubation with BHK-21 cells. To investigate whether the antibodies display neutralizing activity against a lethal RV infection in vivo, we performed a Syrian hamster study by infecting with 50LD(50)/100μl of CVS-11 strain intramuscularly (i. m.) in the gastrocnemius muscle. Three recombinant human mAbs CR57 (I), RV08 (II), RV3A5 (III) and the compatibility triple cocktail showed broad cross-neutralizing reactivity to all 11 RV strains. The cocktail composed of three mAbs CR57 (Ⅰ) RV08 (Ⅱ), RV3A5 (Ⅲ) by neutralizing titers of 1 : 1 : 1 has no less in neutralizing ability against these strains, indicating that no mutual interference between the three antibodies. The cocktail exhibited neutralizing synergistic activity against individual strains(JX08-45,Flury,SRV9).The treatment with CR57,RV08,RV3A5 or the triple combination cocktail alone respectively provided better protection with a survival range of 100%against the lethal RV infection compared HRIG immunized alone. Combined immunization with the vaccine, recombinant mAbs protected hamsters with a survival rate of 100%equally as well as HRIG after exposure to a lethal RV infection. Our results provide more candidates eligible for use in a mAb cocktail aimed at replacing RIG for rabies post-exposure prophylaxis.