EVALUATION OF PROPHYLACTIC EFFICACY OF HUMAN ANTI-RABIES MONOCLONAL ANTIBODIES IN A MOUSE MODEL by CHAKRAVARTHY CHENNAREDDY

Rabies post exposure prophylaxis (PEP) includes administration of both vaccine and anti-rabies immunoglobulin. Rabies immunoglobulins are expensive and available in limited quantities. There is an inherent variability in quality and specificity between batches of immunoglobulin preparations and possibility of contamination with known or unknown pathogens. To provide a cost-effective and safe replacement for currently used human rabies immunoglobulin (HRIG) human anti-rabies monoclonal antibodies (huMAbs) were developed. The present study evaluated the overall prophylactic efficacy of SO57 and SOJB MAbs individually, in a mouse model when used in combination with rabies vaccine and compared with conventional HRIG. When the protective effect of antibodies was examined in mice challenged with CVS-N2C virus, a dose-dependent survivorship response was observed in animals treated with antibodies and no animal survived in the control group. At the highest dose of antibody given 80% survivorship was recorded for SO57 and SOJB antibodies where as only 50% survived with HRIG. Serum half-lives were found to be approximately 16 days for SO57 (IgG1); 11 days for SOJB (IgG3) and 8 days for HRIG (polyclonal). Furthermore, we investigated the potential interference of antibodies on vaccine mediatedimmunity. When compared to the control group which was given only vaccine shots, the groups of animals given both antibody and vaccine developed lower virus neutralizing antibody (VNA) titers. The VNA titers appear to be a function of dose of antibody given and serum half-life of each antibody. The interference, as correlated with VNA titers developed in mice, is comparable to HRIG for both SO57 and SOJB MAbs. When we investigated more on the induction of interference by antibodies on vaccine –mediated immunity with combinations of (i) antibody and different concentrations of vaccine (ii) administration of antibody and vaccine at different time intervals followed by intracerebral (i.c.) challenge all the groups of mice recorded higher survival rates. But the survival rates for SO57 and SOJB were comparable to that of HRIG. Unlike in the previous studies of mouse monoclonal antibodies, we observed that passively administered human monoclonal antibodies and HRIG protects mice against intra cerebral challenge. The protective effect at the point of i.c. challenge may be a synergistic effect of passive and active immunities and account for higher survival among groups. Together this data suggests that human anti-rabies monoclonal antibodies (huMAbs) viz: SO57 and SOJB have potential to replace the currently used human rabies immunoglobulin (HRIG) for rabies post exposure prophylaxis (PEP) regimen.