Characterization of the Monkeypox Virus [MPX]-Specific Immune Response in MPX-Cured Individuals Using Whole Blood to Monitor Memory Response.

Background: Monkeypox (Mpox) is a zoonotic disease caused by monkeypox virus (MPXV), an Orthopoxvirus (OPXV). Since we are observing the first MPXV outbreak outside the African continent, the general population probably does not have a pre-existing memory response for MPXV but may have immunity against the previous smallpox vaccine based on a live replicating Vaccinia strain (VACV). Using a whole blood platform, we aim to study the MPXV- T-cell-specific response in Mpox-cured subjects.

Methods: We enrolled 16 subjects diagnosed with Mpox in the previous 3-7 months and 15 healthy donors (HD) with no recent vaccination history. Whole blood was stimulated overnight with MPXV and VACV peptides to elicit CD4 and CD8 T-cell-specific responses, which were evaluated by ELISA and multiplex assay.

Results: Mpox-cured subjects showed a significant IFN-γ T-cell response to MPXV and VACV. Besides IFN-γ, IL-6, IP-10, IL-8, IL-2, G-CSF, MCP-1, MIP1-α, MIP-1β, IL-1Rα, and IL-5 were significantly induced after specific stimulation compared to the unstimulated control. The specific response was mainly induced by the CD4 peptides MPX-CD4-E and VACV-CD4.

Conclusions: We showed that MPXV-specific responses have a mixed Th1- and Th2-response in a whole blood platform assay, which may be useful for monitoring the specific immunity induced by vaccination or infection.