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. 2024 Aug 26;12(9):964.
doi: 10.3390/vaccines12090964.

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

Elisa Petruccioli  1 , Settimia Sbarra  1 , Serena Vita  2 , Andrea Salmi  1 , Gilda Cuzzi  1 , Patrizia De Marco  2 , Giulia Matusali  3 , Assunta Navarra  4 , Luca Pierelli  5 , Alba Grifoni  6 , Alessandro Sette  6   7 , Fabrizio Maggi  3 , Emanuele Nicastri  2 , Delia Goletti  1
Affiliations

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

Elisa Petruccioli et al. Vaccines (Basel). .

Abstract

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.

Keywords: IFN-γ; MPXV; Mpox.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Alessandro Sette is a consultant for AstraZeneca Pharmaceuticals, Calyptus Pharmaceuticals, Inc., Darwin Health, EmerVax, EUROIMMUN, F. Hoffman-La Roche Ltd., Fortress Biotech, Gilead Sciences, Granite bio., Gritstone Oncology, Guggenheim Securities, Moderna, Pfizer, RiverVest Venture Partners, and Turnstone Biologics. Alba Grifoni is a consultant for Pfizer. Elisa Petruccioli is a consultant for AIFA [Italian Medicines Agency]. Delia Goletti is a consultant for Amgen, Almirall, Astra Zeneca, Biogen, Biomerieux, Eli Lilly, Janssen, PDB Biotec, and Qiagen. The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
MPXV-specific T-cell response from in vitro stimulated samples from Mpox-cured individuals. Graphs report the IFN-γ response induced by MPX-CD4-P; MPX-CD8-P, VACV-CD4, and VACV-CD8 stimulation. Results for the MPX-CD8-P condition were available only for 15 individuals. ELISA was performed on plasma samples from whole blood stimulation, and IFN-γ was expressed as IU/mL; the IFN-γ values of the stimulated conditions were not subtracted from the unstimulated control values. The horizontal lines represent the median; statistical analysis was performed using the Wilcoxon test; black plots refer to HIV-uninfected subjects, and red plots refer to PLWH. Abbreviations: IFN-γ: interferon-γ; HD: healthy donor; PLWH: people living with HIV.
Figure 2
Figure 2
Multiplex analysis of immune factors different from IFN-γ specifically induced after in vitro Mpox peptide stimulation in Mpox-cured subjects. Graphs report the levels of different immune factors in response to MPX-CD4-P; MPX-CD8-P, VACV-CD4, and VACV-CD8 stimulation. The different immune factors were evaluated by Luminex assay in plasma collected after whole blood stimulation, and levels of analytes were expressed as IU/mL. The value of the stimulated condition was not subtracted from the value of the unstimulated control. Among the 27 analytes evaluated, we report only the immune factors with significant modulation between the unstimulated control and peptide stimulation. The horizontal lines represent the median; statistical analysis was performed using the Wilcoxon test; black plots refer to HIV-uninfected subjects, and red plots refer to PLWH. Abbreviations: IFN-γ: interferon-γ; IL: interleukin; IP-10: interferon-γ inducible protein; G-CSF: granulocyte-colony-stimulating factor; MCP-1: monocyte chemoattractant protein-1; MIP-1: monocyte chemoattractant protein-1; IL-1Ra: interleukin-1 Receptor antagonist; PLWH: people living with HIV.
Figure 3
Figure 3
Mpox-specific immune signature based on selected immune factors. (A) The graphs represent the median proportion of immune factors secreted in response to (A) MPX-CD4-P; MPX-CD8-P; (B) VACV-CD4, VACV-CD8. The different immune factors were measured by Luminex assay in plasma collected after whole blood stimulation. The value of the stimulated condition was subtracted from the value of the unstimulated control. Abbreviations: IFN-γ: interferon-γ; IL: interleukin; IP-10: interferon-γ inducible protein; G-CSF: granulocyte-colony stimulating factor; MCP-1: monocyte chemoattractant protein-1; MIP-1: macrophage inflammatory protein-1; IL-1Ra: interleukin-1 Receptor antagonist.
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