Mucker, Eric M, Freyn, Alec W, Bixler, Sandra L, Cizmeci, Deniz, Atyeo, Caroline, Earl, Patricia L, Natarajan, Harini, Santos, Genisis, Frey, Tiffany R, Levin, Rafael H, Meni, Anusha, Asthagiri-Arunkumar, Guha A, Stadlbauer, Daniel, Jorquera, Patricia A, Bennett, Hamilton, Johnson, Joshua ORCID: 0000-0003-0000-5226, Hardcastle, Kath, Americo, Jeffrey L, Cotter, Catherine A, Koehler, Jeff W, Davis, Christopher I, Shamblin, Joshua, Ostrowski, Kristin, Raymond, Jo L, Ricks, Keersten M, Carfi, Andrea, Yu, WenHan, Sullivan, Nancy J, Moss, Bernard, Alter, Galit and Hooper, Jay W (2024) Comparison of protection against mpox following mRNA or modified vaccinia Ankara vaccination in nonhuman primates. Cell, 187 (20). pp. 5540-5553. ISSN 0092-8674

Abstract

In 2022, mpox virus (MPXV) spread worldwide, causing 92,000 mpox cases in 110 non-endemic countries. Modified vaccinia Ankara (MVA) vaccine use reduced transmission in at-risk populations but failed to deliver complete protection. Lag in manufacturing and distribution of MVA resulted in additional MPXV spread, with 12,000 reported cases in 2023 and an additional outbreak in Central Africa of clade I virus. These outbreaks highlight the threat of zoonotic spillover by Orthopoxviruses. mRNA-1769, an mRNA-lipid nanoparticle (LNP) vaccine expressing MPXV surface proteins, was tested in a lethal MPXV primate model. Similar to MVA, mRNA-1769 conferred protection against challenge and further mitigated symptoms and disease duration. Antibody profiling revealed a collaborative role between neutralizing and Fc-functional extracellular virion (EV)-specific antibodies in viral restriction and ospinophagocytic and cytotoxic antibody functions in protection against lesions. mRNA-1769 enhanced viral control and disease attenuation compared with MVA, highlighting the potential for mRNA vaccines to mitigate future pandemic threats.

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