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<p>Data on MPXV-specific T-cell responses at the single-peptide level remain limited in patients with mpox and in MVA-BN vaccinees. Here, we characterized the breadth and specificity of MPXV-specific T-cell responses at the single-peptide level after in vitro expansion with overlapping 20-mer peptides spanning the MPXV proteins H3L, A35R, and B6R. The study included 28 adult males: 15 with a history of mpox (including 6 with additional MVA-BN vaccination), 7 MVA-BN-only vaccinees, and 6 unexposed participants. All mpox and MVA-BN participants responded to at least one H3L peptide, indicating broad immunogenicity, while responses to A35R and B6R were more common in the mpox group. Notably, the breadth of B6R-specific CD4<sup>+</sup> T-cell responses correlated with hybrid immunity (<i>r</i> = 0.6; <i>p</i> = 0.02). Interestingly, MVA-BN and mpox individuals demonstrated distinct immunodominant patterns: H3L_251–270 and H3L_211–230 were mainly recognized among mpox individuals, whereas MVA-BN recognized H3L_221–240 more frequently. High-affinity HLA binding to multiple H3L peptides suggests broad population coverage. Additional immunogenetic analysis revealed a shared TRBV15 clonotype in about 50% of mpox cases. In summary, these findings highlight H3L as a potential vaccine target, guiding the development of next-generation multi-antigen MPXV vaccines to elicit comprehensive T-cell immunity.</p>

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MPXV H3L elicits broadly directed CD4 T cell responses in mpox patients and MVA vaccinees

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月7日

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  • David da Fonseca Araújo,
  • Christoph Schultheiß,
  • Leon Cords,
  • Hendrik Karsten,
  • Robin Woost,
  • Sonja Grobecker,
  • Tim Westphal,
  • Liz Lam,
  • Marc Lütgehetmann,
  • Susanne Pfefferle,
  • Olaf Degen,
  • Sven Peine,
  • Hanna Matthews,
  • Stefan Schmiedel,
  • Guido Schäfer,
  • Hanna-Marie Weichel,
  • Marylyn Addo,
  • Alessandro Sette,
  • John Sidney,
  • Mascha Binder,
  • Christian Hoffmann,
  • Julian Schulze zur Wiesch

摘要

Data on MPXV-specific T-cell responses at the single-peptide level remain limited in patients with mpox and in MVA-BN vaccinees. Here, we characterized the breadth and specificity of MPXV-specific T-cell responses at the single-peptide level after in vitro expansion with overlapping 20-mer peptides spanning the MPXV proteins H3L, A35R, and B6R. The study included 28 adult males: 15 with a history of mpox (including 6 with additional MVA-BN vaccination), 7 MVA-BN-only vaccinees, and 6 unexposed participants. All mpox and MVA-BN participants responded to at least one H3L peptide, indicating broad immunogenicity, while responses to A35R and B6R were more common in the mpox group. Notably, the breadth of B6R-specific CD4+ T-cell responses correlated with hybrid immunity (r = 0.6; p = 0.02). Interestingly, MVA-BN and mpox individuals demonstrated distinct immunodominant patterns: H3L_251–270 and H3L_211–230 were mainly recognized among mpox individuals, whereas MVA-BN recognized H3L_221–240 more frequently. High-affinity HLA binding to multiple H3L peptides suggests broad population coverage. Additional immunogenetic analysis revealed a shared TRBV15 clonotype in about 50% of mpox cases. In summary, these findings highlight H3L as a potential vaccine target, guiding the development of next-generation multi-antigen MPXV vaccines to elicit comprehensive T-cell immunity.