A single-dose nanoparticle vaccine protects against mpox in preclinical models.

Abstract

The ongoing outbreak and emergence of monkeypox virus (MPXV) clade Ib and IIb lineage have heightened its transmissibility, morbidity, and mortality, underscoring the urgent need for safe and effective vaccines against MPXV infection. In this study, we developed a "two-in-one" nanoparticle vaccine, DAM-NP, which incorporates bivalently fused M1 and A35 antigens conjugated to a self-assembled 24-meric ferritin nanoparticle. Preclinical evaluations demonstrated that DAM-NP elicits robust humoral and cellular immune responses, providing complete protection against lethal vaccinia virus challenge. Importantly, pre-existing antibodies resulting from prior infection with the VACV Tiantan strain utilized for smallpox prevention did not diminish vaccine efficacy. A single dose was sufficient to prevent both morbidity and mortality following a lethal MPXV challenge. These findings establish DAM-NP as a highly immunogenic and promising single-dose vaccine candidate for prevention of MPXV and other orthopoxvirus infections.