Assessment of the viral safety of antivenoms fractionated from equine plasma

Abstract

Antivenoms are preparations of intact or fragmented (F(ab')2 or Fab) immunoglobulin G (IgG) used in human medicine to treat the severe envenomings resulting from the bites and stings of various animals, such as snakes, spiders, scorpions, or marine animals, or from the contact with poisonous plants. They are obtained by fractionating plasma collected from immunized horses or, less frequently, sheep. Manufacturing processes usually include pepsin digestion at acid pH, papain digestion, ammonium sulphate precipitation, caprylic acid precipitation, heat coagulation and/or chromatography. Most production processes do not have deliberately introduced viral inactivation or removal treatments, but antivenoms have never been found to transmit viruses to humans. Nevertheless, the recent examples of zoonotic diseases highlight the need to perform a careful assessment of the viral safety of antivenoms. This paper reviews the characteristics of equine viruses of antivenoms and discusses the potential of some manufacturing steps to avoid risks of viral contamination. Analysis of production parameters indicate that acid pH treatments and caprylic acid precipitations, which have been validated for the manufacture of some human IgG products, appear to provide the best potential for viral inactivation of antivenoms. As many manufacturers of antivenoms located in developing countries lack the resources to conduct formal viral validation studies, it is hoped that this review will help in the scientific understanding of the viral safety factors of antivenoms, in the controlled implementation of the manufacturing steps with expected impact on viral safety, and in the overall reinforcement of good manufacturing practices of these essential therapeutic products.

Snakebite Envenoming: A Public Health Perspective

“…LARs are treated with anti-histamines and steroids. Another aspect of antivenom safety that has to be considered is microbial safety, which is guaranteed by sterile filtration of the final product and the use of viral inactivation/removal steps (Burnouf et al, 2004;WHO, 2010a). Some of the manufacturing steps currently used in antivenom production inactivate or remove viruses, thus contributing to the microbial safety of these products (Burnouf et al, 2004;WHO, 2010a).…”

Improvement of purification methods for F(ab')2 fraction of equine hyperimmune plasma against scorpion venom

“…There are numerous of harmful viruses of equine source: Equine Infectious Anaemia Virus, a lentivirus of the same family as HIV, influenza and Japanese Encephalitis or Venezuelan Equine Encephalitis Virus. It could be useful if the process accustomed to make antivenoms could eliminate or inactivate probably types of virus pollution [28]. In this regard, the fractionation identified here regarding pepsin digestion and also treatment with caprylic acid might inactivate several viruses because of the acidic situation and the detergent action of the organic acid [14].…”

Biotechnological tools for diagnosis of equine infectious diseases

“…On various occasion equines are used for various purposes such as ceremonies, riding, sports, draught racing, transport and antitoxin/antibody production, throughout the world (Burnouf et al, 2004). There is possibility of disease transmission and spread at the time of equines movement from one country to another.…”