Scientists at The Pirbright Institute have used genetic engineering to develop a vaccine that protects birds against both Marek’s disease and avian influenza, also known as bird flu.

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 new 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 Prof. 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.

How it works

Mutations can occur with high frequency in HA proteins, enabling flu 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 lab 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.

Image shows clumps of red blood cells forming around cells infected by the HVT vaccine virus, indicating that the bird flu HA has been successfully incorporated in the vaccine.

This study was supported by grants funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation (UKRI) under Newton Fund UK-China-Philippines-Thailand Swine and Poultry Research Initiative, Zoonoses and Emerging Livestock Systems (ZELS) and the British Council Newton Fund Institutional Links programme.