MPOX-directed T cell responses
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 CD4+ and CD8+ 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 resolved or acute mpox, 7 MVA-BN-only vaccinees, and 6 unexposed participants serving as negative controls. In the mpox group, 6 individuals had also been vaccinated with MVA-BN before joining the study, forming a hybrid group. All participants in the mpox and MVA-BN groups responded to at least one H3L peptide, indicating broad immunogenicity, while responses to A35R and B6R were more common in the mpox group and less frequent among MVA-BN-only vaccinees. Notably, the breadth of B6R-specific CD4+ T-cell responses correlated with hybrid immunity (r = 0.6; P = 0.02). Seven H3L and one A35R peptide elicited virus-specific CD4+ T-cell responses in at least 20% of subjects, with distinct immunodominant patterns: H3L_251–270 and H3L_211–230 were mainly recognized among mpox individuals, whereas H3L_221–240 was more often recognized in MVA-BN vaccinees. High-affinity binding of individual HLA molecules to multiple immunogenic H3L peptides suggests broad coverage across populations. 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 and reveal infection-driven responses to A35R and B6R that are more detectable in individuals recovering from natural MPXV infection, potentially guiding the development of next-generation multi-antigen MPXV vaccines to elicit comprehensive T-cell immunity.
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 CD4+ and CD8+ 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 resolved or acute mpox, 7 MVA-BN-only vaccinees, and 6 unexposed participants serving as negative controls. In the mpox group, 6 individuals had also been vaccinated with MVA-BN before joining the study, forming a hybrid group. All participants in the mpox and MVA-BN groups responded to at least one H3L peptide, indicating broad immunogenicity, while responses to A35R and B6R were more common in the mpox group and less frequent among MVA-BN-only vaccinees. Notably, the breadth of B6R-specific CD4+ T-cell responses correlated with hybrid immunity (r = 0.6; P = 0.02). Seven H3L and one A35R peptide elicited virus-specific CD4+ T-cell responses in at least 20% of subjects, with distinct immunodominant patterns: H3L_251–270 and H3L_211–230 were mainly recognized among mpox individuals, whereas H3L_221–240 was more often recognized in MVA-BN vaccinees. High-affinity binding of individual HLA molecules to multiple immunogenic H3L peptides suggests broad coverage across populations. 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 and reveal infection-driven responses to A35R and B6R that are more detectable in individuals recovering from natural MPXV infection, potentially guiding the development of next-generation multi-antigen MPXV vaccines to elicit comprehensive T-cell immunity.