Provided herein are recombinant poxviruses comprising heterologous or native nucleic acids specifying excess double-stranded RNA (dsRNA) early in infection, which may further comprise heterologous nucleic acids encoding one or more costimulatory molecules, and/or heterologous nucleic acids encoding one or more infectious disease-associated antigens or tumor-associated antigens, as well as pharmaceutical compositions comprising such recombinant poxviruses and methods and uses thereof. The recombinant poxviruses provided herein enhance innate and adaptive immune activation in subjects compared to identical recombinant poxviruses lacking heterologous or native transcription units specifying excess early dsRNA.

The present disclosure provides methods for producing a vaccine composition containing a pathogen that is rendered noninfectious by exposure to hydrogen peroxide. The methods disclosed herein are suitable for the preparation of vaccines for a wide variety of pathogens, including viruses, bacteria and parasites. The disclosure also provides vaccine compositions (medicaments) containing a pathogen inactivated by exposure to hydrogen peroxide. Methods for eliciting an immune response in a subject by administering vaccine compositions containing a hydrogen peroxide inactivated pathogen are also provided.