Comparative Neutralization Activity of Commercial Rabies Immunoglobulin against Diverse Lyssaviruses

Novel lyssaviruses, the causative agents of rabies, continue to be described mostly due to increased surveillance in bat hosts. Biologicals for the prevention of rabies in humans have, however, remained largely unchanged for decades. This study aimed to determine if commercial rabies immunoglobulin (RIG) could neutralize diverse lyssaviruses. Two commercial preparations, of human or equine origin, were evaluated against a panel consisting of 13 lyssavirus species. Reduced neutralization was observed for the majority of lyssaviruses compared to rabies virus and was more evident for lyssaviruses outside of phylogroup I. Neutralization of more diverse lyssaviruses only occurred at very high doses, except for Ikoma lyssavirus, which could not be neutralized by the RIG evaluated in this study. The use of RIG is a crucial component of rabies post-exposure prophylaxis and the data generated here indicate that RIG, in its current form, will not protect against all lyssaviruses. In addition, higher doses of RIG may be required for neutralization as the genetic distance from vaccine strains increases. Given the limitations of current RIG preparations, alternative passive immunization options should be investigated.