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

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Monkeypox (Mpox) is a zoonotic disease caused by the monkeypox virus (MPXV), an Orthopoxvirus (OPXV).
• The recent global MPXV outbreak highlighted a lack of pre-existing population immunity, though some cross-immunity may exist from prior smallpox vaccination (Vaccinia virus, VACV).
• Understanding T-cell responses in Mpox-cured individuals is crucial for assessing immunity.

Purpose of the Study:

• To investigate the T-cell-specific immune response to MPXV in individuals who have recovered from Mpox.
• To compare T-cell responses to MPXV and VACV peptides in Mpox-cured subjects.
• To evaluate the utility of a whole blood assay for monitoring MPXV-specific immunity.

Main Methods:

• Enrolled 16 Mpox-cured subjects and 15 healthy donors (HD).
• Stimulated whole blood ex vivo with MPXV and VACV peptides.
• Assessed CD4 and CD8 T-cell responses using ELISA and multiplex assays, measuring cytokine induction.

Main Results:

• Mpox-cured subjects demonstrated significant interferon-gamma (IFN-γ) T-cell responses to both MPXV and VACV.
• Elevated levels of multiple cytokines (IL-6, IP-10, IL-8, IL-2, G-CSF, MCP-1, MIP1-α, MIP-1β, IL-1Rα, IL-5) were observed post-stimulation.
• The primary T-cell response was mediated by CD4 peptides, specifically MPX-CD4-E and VACV-CD4.

Conclusions:

• MPXV-specific immune responses in Mpox-cured individuals exhibit a mixed Th1 and Th2 profile.
• The findings suggest that whole blood assays can effectively monitor specific immunity post-MPXV infection or vaccination.
• This research provides insights into the adaptive immune response to Mpox virus.