Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

Post-exposure prophylaxis (pep) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. since anti-rabies immune globulins are expensive and scarce,there is a need for cheaper alternatives that can be produced more consistently. previously,we generated potent virus-neutralising vhh,also called nanobodies,against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. the vhh domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. in the current study we evaluated the efficacy of half-life extended anti-rabies vhh in combination with vaccine for pep in an intranasal rabies infection model in mice. the pep combination therapy of systemic anti-rabies vhh and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies vhh alone,prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate),when treated 24 hours after rabies virus challenge. vaccine alone was unable to rescue mice from lethal disease. as reported also for immune globulins,some interference of anti-rabies vhh with the antigenicity of the vaccine was observed,but this did not impede the synergistic effect. post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. anti-rabies vhh and vaccine act synergistically to protect mice after rabies virus exposure,which further validates the possible use of anti-rabies vhh for rabies pep. © 2016 terryn et al.