African swine fever virus binding proteins identification using a pig macrophages membrane protein library

Project summary

The African swine fever (ASF) pandemic, a haemorrhagic pig disease with mortality rates of up to 100%, is currently spread in four continents: Asia, Africa, Europe and America. Even with the application of biosecurity and movement control measures, the disease is advancing to new regions every day. ASF is not only affecting the big international pig producers with astronomic economic losses but also hampering the possibility of countries like Uganda to build a strong pig industry and the smallholder farmers in LMICs, with mostly backyard production systems, to make a living out of it, with women and the youth being the most affected. Developing a safe and robust vaccine will provide an effective control measure for this devastating disease. Although it is long known that

ASF virus (ASFV), the causative agent of ASF, targets pig monocytes/macrophages, the receptors involved in virus binding are yet to be fully characterized, and the viral proteins involved in attachment and internalization have only been partially identified; this knowledge gap prevents a rational vaccine design. Currently, the research community is focused on developing live attenuated recombinant vaccines that, even effective, pose biosecurity concerns. Subunit vaccines, based on non-infective parts of the virus, are a much safer alternative. However, there are no consistent published results on efficacy, even when using the same antigens, ranging from partial protection to no-protection or even disease enhancement.

In this project, we will identify new ASFV binding proteins and their host cell receptors using arrayed heterologous expression of membrane proteins from ASFV permissible pig monocyte/macrophages in refractory human fibroblasts. The cells will be exposed to ASFV to identify membrane proteins that allow ASFV to attach and invade the refractory human fibroblasts. The identified proteins will be considered as potential antigens for a future subunit vaccine.