Immunological signatures and genomic adaptations in Human Mpox Clade Ib and IIb and Buffalopox Infections in India

Mpox and buffalopox are zoonotic viral infections which demonstrate distinct clinical and immune profile. This study examines the clinical presentation with genomic and immunological characteristics among three confirmed cases of Mpox Clade IIb-A.2.1 and Clade Ib infections and a buffalopox from Malappuram, Kerala, India.

Immunophenotyping via flow cytometry was used to assess T, B, Natural Killer (NK) cells, and monocytes. The viral DNA, Anti-Mpox IgG/IgM, and anti-BPXV IgG were detected using real time PCR and ELISA respectively. Genomic characterization was performed using next generation sequencing. MAFFT alignment and IQ-TREE2 with maximum likelihood method was used for phylogenetic analysis.

Clinically, vesiculo-pustular lesions detected in Mpoxv infection were more severe in Clade Ib patient along with penile edema and gangrenous eschar. The face and hands were primarily affected in BPXV infection. Immunological analysis demonstrated notable differences where Mpoxv infection exhibited major increase in lymphocytes and NK cells and differential activation patterns of immune T-cell population. During BPXV infection, B-cell numbers rose with expansion of mucosal-homing B-cells. IgM and IgG responses differed among infections, where Mpoxv Clade Ib generated early but transient IgM and low IgG titer, while Clade IIb-A.2.1 and BPXV exhibited prolonged IgG response. Genomic analysis revealed deletion in diagnostic region in Clade Ib, albeit Clade IIb showed host-derived mutations. The multiple genomic alignments revealed distinct immunological responses and vaccine development capacity of orthopoxviruses.

The findings of the study emphasizes the need for extensive genomic surveillance and immunological research. This will help in understanding the pattern of virus evolution and host immune responses in orthopoxvirus infections.