Comparative Neutralization Activity of Commercial Rabies Immunoglobulin against Diverse Lyssaviruses

Abstract

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.

Eco-evolutionary dynamics of pathogen immune-escape: deriving a population-level phylodynamic curve

“…Finally, and perhaps most importantly, our highly idealized model does not include any detailed antigenic fitness landscape. Studies on the relation between antigenic and genomic distance suggest a correlation between the two [72,73], while antigenic cartography indicates that variants are typically well-separated in antigenic space [74][75][76][77]. Both of these findings challenge the memory-less constant-rate process assumption we make in this paper.…”

Molecular Characterization of Lyssaviruses Originating from Domestic and Wild Cats Provides an Insight on the Diversity of Lyssaviruses and a Risk of Rabies Transmission to Other Susceptible Mammals and Humans in South Africa

“…Rabies virus infection and subsequent disease in humans can be prevented through the prompt application of rabies post-exposure prophylaxis (PEP). The management of human contact cases is currently done with strict adherence to the WHO rabies PEP guidelines [43], resulting in close to 100% efficacy [43]. The use of rabies immunoglobulin (RIG) is recommended in all category III exposures, i.e., single or multiple transdermal bites or scratches, contamination of mucous membranes or broken skin with saliva from animal licks, and exposures due to direct contact with bats [44].…”

“…The diversity of lyssavirus species has more than doubled over the years, with a growing concern for the efficacy of the currently available biologicals against the range of viruses that are antigenically distinct from RABV. In a recent study, two commercial rabies immunoglobulins (RIG) prepared from human, or equine (ERIG) blood plasma were evaluated against a panel of 13 diverse lyssavirus species [43]. The study showed a reduced neutralization for the majority of lyssaviruses compared to rabies virus, particularly for lyssaviruses in phylogroups II and III [43].…”

“…In a recent study, two commercial rabies immunoglobulins (RIG) prepared from human, or equine (ERIG) blood plasma were evaluated against a panel of 13 diverse lyssavirus species [43]. The study showed a reduced neutralization for the majority of lyssaviruses compared to rabies virus, particularly for lyssaviruses in phylogroups II and III [43]. Furthermore, neutralization of more diverse lyssaviruses only occurred at very high virus doses, except for Ikoma lyssavirus, which could not be neutralized by the RIG evaluated in this study.…”

“…At the time of the report, the child remained well. The use of RIG is, therefore, a crucial component of rabies post-exposure prophylaxis, but RIG, in its current form, appears not to protect against all lyssaviruses [43]. In addition, higher doses of RIG may be required for neutralization as the genetic distance from vaccine strains increases.…”