Inactivation of West-Nile virus during peptic cleavage of horse plasma IgG.

This research investigates the inactivation of the West-Nile virus (WNV) during the peptic cleavage of horse plasma IgG, a process used in producing antivenins and antitoxins for human use. The study finds that this method can effectively remove or inactivate potential viral contaminants, thus ensuring the safety of the resulting F(ab)(2) products.

Introduction to Peptic Cleavage of Horse Plasma IgG

• This is a process used in the production of F(ab)(2) products, such as antivenin and antitoxin for human use.
• It involves the enzymatic cleavage of the IgG molecule at a low pH, which removes the Fc fragment from the molecule.
• The removal of the Fc fragment results in fewer side effects of the F(ab)(2) product when used for passive immunotherapy as compared to the whole IgG molecule.

Need for Viral Inactivation

• The plasma used in this procedure can be contaminated with zoonotic horse viruses, such as West-Nile Virus, making it necessary to remove or inactivate these contaminants.
• Regulatory bodies like the Commission for Plasma-Derived Medical Products (CPMP) and the Committee for Proprietary Medical Products have published guidelines for carrying out such studies.
• These guidelines recommend performing viral clearance studies on scaled-down production processes that are suspected to contribute to virus clearance, using a spiked model virus in the starting material.
• The chosen model virus should be non-pathogenic but genetically similar to the potential infective virus.

Method for Quantifying Virus Clearance

• Virus clearance is determined by quantifying the amount of virus in the product before and after the production process.
• Results showing log(10) reductions of around 4 logs or more, as well as a biphasic inactivation curve (a fast initial phase followed by a slower phase), suggest successful virus clearance with the test virus under investigation.

Results and Implications

• The study’s findings suggest that the peptic cleavage of horse plasma IgG can successfully remove or inactivate the West-Nile virus, making it a viable method in the production of safe F(ab)(2) products.
• This research contributes to the broader knowledge of viral inactivation, particularly in the context of producing plasma-derived medical products.
• While the method is shown to be effective against the West-Nile virus in this study, further research will be needed to understand its efficacy in inactivating other potential viral contaminants.