Abstract
The upsurge of mpox (formerly known as monkeypox) in Africa and its global spread highlight the need for improved vaccines. The development of new recombinant vaccines, including mRNA and protein nanoparticles, depends on understanding the biology of poxviruses and selecting the most protective immunogens. Animal studies demonstrate that vaccines need to target the antigens of both infectious forms - the mature virion and the enveloped virion - which display surface proteins responsible for cell entry and cell-to-cell spread, respectively. Although some of these proteins have been shown to induce protective antibodies, others including most of those that are essential for membrane fusion remain to be tested. We review the structures of orthopoxvirus surface proteins as a guide to the selection of optimal antigens for recombinant vaccines.