Studies undertaken at The Pirbright Institute in collaboration with Inovio Pharmaceuticals have shown that pigs can be used to assess whether influenza antibody therapies are effective, which could provide a better indication of their success in humans than small animal trials. They also demonstrated pigs are suitable for analysing the delivery systems used to administer the antibodies in order to provide longer lasting protection.
Having been successfully utilised for Ebola virus and respiratory syncytial virus, the use of antibodies to provide protection and reduce symptoms of influenza is an area of great interest. Although several influenza antibodies have progressed to clinical trials based on their success in small animals (ferrets and mice), the outcome has been disappointing as no antibodies have shown therapeutic effect in humans.
A previous study by Pirbright showed that pigs are good models for influenza vaccine studies as they are naturally infected by the same subtypes of influenza viruses as humans, have similar immune systems and are more comparable in size and physiology than smaller animals.
The team’s new research, published in the Journal of Immunology established that a human antibody (2-12C) can neutralise the H1N1 2009 flu pandemic virus in pigs, thereby providing protection. Both the amount of virus and signs of infection in the lungs were reduced in pigs that received treatment.
Alongside testing the efficiency of 2-12C, the team also assessed a new antibody delivery method that works by administering the antibody genes to pigs. Once inside pig cells, the genes continuously generate antibodies, providing longer term protection than a single direct inoculation of antibodies. The team showed that this gene delivery method for 2-12C was able to protect pigs from signs of disease typically caused by H1N1.
The success of this antibody and delivery platform in the pig model indicates that these treatments could potentially also work in humans. The pig provides an excellent intermediate step between trials in smaller animals and humans and could provide more accurate assessments of antibody therapies against influenza.
Dr Elma Tchilian, Head of the Mucosal Immunology Group at Pirbright said: “We are very excited that the pig model is becoming useful for testing and refining antibody treatments for life threatening influenza infections and could be equally useful for other infectious diseases.”
This research was funded by the Bill & Melinda Gates Foundation, the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation (UKRI) and the National Institute of Allergy and Infectious Diseases, part of the U.S. National Institutes of Health.