(848) Monoclonal antibody therapy for rabies disease: long term impact on central nervous system recovery

Introduction/Rationale: Lyssaviruses are the causative agent for rabies, a disease that is uniformly fatal in humans without post-exposure prophylaxis (PEP). Once infection reaches the central nervous system (CNS), PEP is no longer effective. Using a mouse model of lethal rabies disease, we previously demonstrated that peripheral administration of a single dose of neutralizing human monoclonal antibody (mAb), A6, which targets the viral glycoprotein, is highly effective at protecting against lethality. Notably, A6 is effective even when administered following robust replication of virus in the CNS. Moreover, A6 is effective at reducing or even fully reversing multiple signs of disease, including weight loss and limb paralysis.

Methods: Motor function analyses demonstrated improved motor function of infected A6-treated animals compared to infected untreated controls during the acute phase of disease, but significant impairment compared to uninfected control animals over the post-recovery phase, even months post-treatment. In this study, we perform immunohistochemistry on tissue samples collected at multiple time points post-infection to investigate the underlying mechanisms that may account for failure to completely recover motor function.

Results: Via stains for inflammatory markers of blood brain barrier (BBB) integrity, initial findings suggest diminished BBB function in both infected untreated animals and infected A6-treated animals.

Conclusion: These findings corroborate previous data that have suggested structural damage to the CNS, and further suggest that elements of this damage may be beyond repair, despite rescue from mortality and partial functional recovery.