Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.
Authors: Kim Pan Kyeom, Keum Sun Ju, Osinubi Modupe O V, Franka Richard, Shin Ji Young, Park Sang Tae, Kim Man Su, Park Mi Jung, Lee Soo Young, Carson William, Greenberg Lauren, Yu Pengcheng, Tao Xiaoyan, Lihua Wang, Tang Qing, Liang Guodong, Shampur Madhusdana, Rupprecht Charles E, Chang Shin Jae
Journal: PloS one
Summary
# Editorial Summary Rabies post-exposure prophylaxis currently relies on human or equine immune globulin products, which face significant challenges around supply, cost, safety and effectiveness—prompting research into monoclonal antibody alternatives. Researchers screened existing hybridomas from the US CDC to develop two chimeric human monoclonal antibodies (#7 and #17) targeting different antigenic sites on the rabies virus; these were engineered by combining variable regions from high-performing hybridomas with constant regions from human antibodies to improve clinical compatibility. Both antibodies demonstrated broad-spectrum neutralisation capacity against 51 field rabies isolates collected across Asia, Africa, North America, South America and Australia, with in vivo testing in Syrian hamster and mouse models showing potent viral neutralisation and a favourable safety profile with minimal immunogenicity concerns. The findings suggest chimeric monoclonal antibodies could offer a more reliable, safer alternative to traditional post-exposure prophylaxis, potentially improving treatment outcomes in horses exposed to rabies and reducing dependence on animal-derived immune globulin products. For equine practitioners, this development may eventually translate into improved rabies management protocols, though clinical trials and regulatory approval would be necessary before implementation in veterinary practice.
Read the full abstract on PubMed
Practical Takeaways
- •This research addresses a critical gap in rabies post-exposure prophylaxis by developing antibodies that could potentially replace limited equine-derived immune globulin supplies
- •Broad-spectrum neutralization across geographically diverse virus isolates suggests potential for universal post-exposure treatment protocols
- •Development of humanized monoclonal antibodies may improve safety and accessibility of rabies prophylaxis compared to current animal-derived products
Key Findings
- •Two chimeric monoclonal antibodies (#7 and #17) successfully neutralized 51 field isolates of rabies virus from multiple continents (Asia, Africa, North America, South America, Australia)
- •Chimeric antibodies bound to antigenic sites III and I/IV with broad-spectrum neutralization capacity
- •In vivo testing in Syrian hamster and mouse models demonstrated high efficacy with low risk of adverse immunogenicity