Glyco-Engineered Plant-Produced Rabies mAbs: A Promising Alternative to RIG

What is it about?

A team of researchers has developed plant-made anti-rabies monoclonal antibodies (mAbs) as a potential alternative to Rabies Immune Globulin (RIG), which has limitations such as limited availability and potential contamination with bloodborne pathogens. The study tested two mAbs, E559 and 62-71-3, expressing high levels of recombinant mAbs in Nicotiana benthamiana glycosylation mutants using a viral-based transient expression system. The plant-made mAbs were found to be structurally sound, efficiently neutralizing diverse rabies virus variants in vitro, and providing enhanced protection against rabies virus compared to human RIG in a hamster model post-exposure challenge trial. These results provide a basis for the development of a multi-mAb based alternative to RIG, which could offer a safer and more affordable option for preventing rabies. However, the biggest barrier to further development and implementation in the clinic is the complicated regulatory pathway for replacement products for lethal but neglected infectious diseases like rabies. The researchers suggest a coordinated global effort to encourage regulatory reform to address this challenge.

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Why is it important?

This research is important because rabies is a life-threatening disease that can be prevented with effective post-exposure prophylaxis (PEP), but the current treatment options have limitations. Human Rabies Immune Globulin (RIG) is the standard component of PEP, but it has restrictions such as limited availability, batch-to-batch inconsistencies, and potential contamination with bloodborne pathogens. Developing an alternative to RIG that is safe, effective, and readily available is crucial for improving public health. Key Takeaways: 1. Rabies is a neglected zoonotic disease that can be prevented effectively by prompt administration of post exposure prophylaxis. 2. Human RIG suffers from many restrictions, making the development of an alternative essential. 3. Anti-rabies monoclonal antibodies (mAbs) have been identified as a promising alternative to RIG. 4. The plant-made mAbs E559 and 62-71-3 were shown to be effective in neutralising diverse rabies virus variants and provided enhanced protection compared to human RIG in a hamster model post-exposure challenge trial. 5. The results provide the basis for the development of a multi-mAb based alternative to RIG.