In 2022-2023, an unprecedented global outbreak of Monkeypox virus (MPXV), a double-stranded DNA virus related to smallpox, emerged in non-endemic areas, causing over 87,000 reported cases in 170 countries. This prompted the WHO to classify it as a Public Health Emergency of International Concern (PHEIC). France alone documented 5,014 cases, with 83% confirmed biologically.
The outbreak strain, responsible for the 2022-2023 epidemic, was identified as the West African B.1 lineage Clade 2b, known as 'mpox”.This outbreak was characterized by its rapid global spread, unique clinical symptoms, and high prevalence among men who have sex with men (MSM). Transmission of mpox can occur through various forms of contact, but sexual contact plays a significant role, with over 91% of cases linked to it. Lesions in genital, perianal, and oral areas suggest sexual transmission, and MPXV DNA has been found in the semen of infected patients.
No specific mpox vaccines exist, but previous evidence indicates that smallpox vaccines can provide some protection due to cross-reaction. JYNNEOSTM, a live, non-replicating Modified Vaccinia Ankara (MVA)-based vaccine, was recently approved for mpox prevention but showed varying efficacy against the 2022 outbreak, highlighting the need for more effective vaccines.
Our understanding of mpox pathogenesis, immunity, and transmission is limited, especially during the recent outbreak. To address these questions, a study using cynomolgus macaques as a model to simulate mucosal MPXV infection with the current outbreak strain is proposed.
The project has two main aims:
1) Elucidate the mechanisms of mpox pathogenesis and the immune response to natural infection using a non-human primate (NHP) model of sexual transmission.
2) Assess the immune response elicited by the currently available MVA vaccine, and identify novel mechanisms that future vaccine candidates may need to activate in order to enhance vaccine effectiveness and improve the immune response to vaccination.
The PhD candidate will receive comprehensive training in theoretical and practical aspects of immunology, virology, and microbiology. This includes experimental techniques for studying virus transmission and the host's immune response to natural infection and vaccination. In addition, the student will gain proficiency in a wide range of techniques, such as cell/tissue cultures, flow cytometry, histology, transcriptomic, and more, using both in vitro and in vivo approaches with an NHP model.
Overall, this project aims to deepen our understanding of mpox pathogenesis and immunity, guide vaccine development, and contribute to public health efforts in combating this emerging infectious disease.