Genetic engineering speeds up poultry vaccine development

Scientists at The Pirbright Institute have used genetic engineering to develop a vaccine that protects birds against both Marek’s disease and avian influenza. They say the process is faster and more efficient compared to previous methods, which will allow poultry vaccine producers to rapidly update vaccine strains in order to keep up with virus evolution.

In a study published in the journal Vaccines, the team used the gene editing tool CRISPR/Cas9 to insert an avian influenza gene into the turkey herpesvirus (HVT) that is used in Marek’s disease vaccines. The gene codes for haemagglutinin (HA), an influenza protein that is key for virus entry into host cells and is therefore an important target of the host immune response to block infection.

“HVT is already widely used in vaccines against Marek’s disease and can be administered to eggs, enabling automated delivery and providing birds with protection from the day they hatch. The additional HA gene we have incorporated will be expressed by HVT when it replicates in host cells, meaning that a single dose of vaccine induces immunity against both viruses”, explained Professor Munir Iqbal, Head of the Avian Influenza group at Pirbright.

“The genetic engineering process we have developed using CRISPR/Cas9 is far quicker and more efficient than previous technologies, as well as being very consistent and accurate. These attributes are essential for providing fast and reliable vaccine production to protect poultry”, Prof Iqbal added.

Mutations can occur with high frequency in HA proteins, enabling influenza viruses to evade immunity generated by vaccines. Using CRISPR/Cas9 to create new vaccines will help tackle evolving viruses by reducing the time it takes manufacturing companies to adapt their vaccine strains to match these mutations, allowing faster responses to outbreaks and providing better protection.

Although this gene editing method is very reliable, a small number of HVT viruses fail to incorporate the HA gene into their own genome effectively. To ensure HA is being expressed in the vaccine, the team exploited the HA protein’s ability to bind to molecules on the surface of red blood cells.

Chicken cells infected with the successfully modified HVT virus express HA on their surface which red blood cells attach to, forming a clump that can be visualised using microscopy. This simple test improves the speed at which suitable vaccine candidates can be identified and has a much broader application as it can also be used for other viruses that incorporate proteins which interact with red blood cells.

“Improving how we make vaccines is critical for preventing avian influenza outbreaks. Our work could help reduce the spread of disease between birds and reduce the risk of infection for people who work closely with poultry”, Prof Iqbal said. “Now that we have developed a rapid method for generating this modified vaccine, our next steps will be to study the vaccine’s effectiveness in field trials.”

Article: Chang, P., Ameen, F., Sealy, J.E., Sadeyen, J.R., Bhat, S., Li, Y., Iqbal, M. (2019). Application of HDR-CRISPR/Cas9 and Erythrocyte Binding for Rapid Generation of Recombinant Turkey Herpesvirus-Vectored Avian Influenza Virus Vaccines. Vaccines 7(4) 192, doi: 10.3390/vaccines7040192

[SOURCE: The Pirbright Institute]