Scientists have taken important steps towards the potential future development of a live vaccine for African swine fever (ASF).
A study, led by thet the Pirbright Institute, the world-leading centre of excellence in research and surveillance of livestock viruses, and published in mBio, uses a novel strategy to make a modified live vaccine safer by reducing its persistence in blood but maintaining its ability to induce a strong protective immune response.
Dr Linda Dixon, and Dr Ana Reis Group Leader and Research Fellow in ASFV at Pirbright, collaborated with Dr Simon Davis, University of Oxford Immunology Network and Dr Shinji Ikemizu, Faculty of Life Sciences at Kumamoto University in Japan.
The team focused on the EP402R gene of ASFV, which encodes the CD2v glycoprotein found in the virus’s external envelope. CD2v helps the virus to bind to erythrocytes (red blood cells), prolonging virus persistence and facilitating transmission.
By using a combination of advanced protein structure modelling and mutagenesis techniques, they identified specific amino acids in CD2v that mediate its interaction with erythrocytes.
“In this study, we characterised the interaction between the ASFV CD2v protein and erythrocytes,” said Dr Dixon. “The interaction plays a key role in viral persistence in blood and can help the virus to “hide” from the host immune system. We identified the amino acids in the viral protein that mediate the interaction and used this information to construct a mutant virus that is no longer able to bind to red blood cells but still expresses the immunogenic CD2v protein.”
Pigs immunised with the modified virus developed strong antibody and cellular immune responses, exhibited mild clinical signs, and showed high levels of protection against subsequent challenge with the wild-type ASFV.
“Our study represents an important step forward in our understanding of ASFV’s interaction with its host. Targeting the virus’s ability to persist in the bloodstream without reducing the protective immune response offers a promising approach to the development of safer and more effective modified live vaccines,” said Dr Dixon.
The research team is now focused on applying the same approach to other virus strains and investigating the host proteins that CD2v interacts with.
ASFV has been present in sub-Saharan Africa for over than 100 years. In 2007, it spread to Georgia in the Caucasus region, initiating a pandemic that has since reached Russia, parts of Europe, and China by 2018, as well as nearly all Asian countries, parts of Oceania, and the Caribbean.
The deadly pig virus is difficult to control in part due to lack of vaccines.