DECIPHER-MPOX

The challenge

During the mpox outbreak in sub-Saharan Africa, exposure to an infected individual may or may not lead to a new infection. Furthermore, when infected, an individual may show no symptoms, experience mild illness, or develop severe disease. It is unclear what factors account for these varying outcomes.

The project

To address this question, the DECIPHER-MPOX project is establishing cohorts of family contacts of infected patients. By tracking them over time and comparing those who fall ill with their immediate family relatives (father, mother or siblings), the project aims to identify factors associated with acquiring mpox infection and with more severe disease.

The project is using a variety of technologies to explore host-related factors associated with mpox susceptibility or resistance. These include:

• Whole exome sequencing, which may reveal rare genetic variants having a major impact on susceptibility.
• Transcriptomics, which may identify common variants or signatures of gene activity, across multiple genes, that are associated with symptom severity.
• Digital cell sorting, which could reveal differences in immune cell populations associated with disease severity.
• Viral genome sequencing to identify variations (strains) within the dominant clade 1b.
• Immunological assays to cross validate phenotypes of monkeypox virus (MPXV) specific host antibody expression, T cell response and or innate function and how they relate to all the above. 

Infectiousness and the impact of infection may also be related to properties of the mpox virus. The project will therefore sequence mpox virus isolates to explore links between genetic changes in the virus and its impacts on human hosts.

The research will be carried out in the Kamituga area of South Kivu Province, Democratic Republic of the Congo (DRC), where the newly detected clade Ib strain of mpox is circulating.

DECIPHER-MPOX is one of nine projects funded through an emergency call for proposals launched in response to the mpox outbreak in the DRC and other sub-Saharan African countries, which was declared a Public Health Emergency of International Concern (PHEIC) by WHO and a Public Health Emergency of Continental Security (PHECS) by Africa CDC in 2024.

Impact

The DECIPHER-MPOX project will provide answers to key virological questions. It will:

• Identify host and virus factors associated with severe disease.
• Help to guide patient care based on the risk of severe disease.
• Provide information on disease mechanisms, which will feed into the development of mpox therapeutics.
• Shed light on potential immunological correlates of protection to inform vaccine development.

Ultimately, a deeper understanding of how contacts are affected following mpox exposure will provide critical evidence to underpin vaccine and therapeutic development, generating new options to prevent and treat mpox disease.