Under this IAA, research will be conducted on a combination of 4 genes that provide a high level of protection in animal models of poxvirus disease (e.g., lethal vaccinia intranasal challenge in mice and lethal monkeypox virus intravenous challenge in nonhuman primates). The gene combination, called 4pox, targets the two infectious forms of poxviruses, the intracellular mature virion (IMV) and the extracellular enveloped virion (EEV).