Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.

Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.

Disclosed herein are recombinant CMV vectors comprising heterologous antigens and microRNA recognition elements to silence expression of CMV genes in the presence of microRNA derived from myeloid cells, an active UL128 protein and an active UL130 protein. Also disclosed are recombinant CMV vectors comprising heterologous antigens and microRNA recognition elements to silence expression of CMV genes in the presence of microRNA derived from myeloid cells, an inactive UL128 protein and an inactive UL130 protein. Also disclosed are methods of generating an unconventional immune response using these vectors. Such an immune response is characterized by generation of a CD8+ T cell response that is predominantly restricted by MHC-II.

The present invention provides an efficient process for culturing viruses in the presence of an endonuclease and for producing vaccines, typically from live attenuated viruses, under conditions to reduce the presence of host cell DNA and eliminate the need for a post-harvest DNA digestion step.

The present invention is related to a beta-herpesvirus, wherein the beta-herpesvirus is spread-deficient.

The present disclosure relates to recombinant rhesus cytomegalovirus (RhCMV) and human cytomegalovirus (HCMV) vectors encoding heterologous antigens, such as pathogen-specific antigens or tumor antigens, which may be used, for example, for the treatment or prevention of infectious disease or cancer. The recombinant RhCMV or HCMV vectors elicit and maintain high level cellular immune responses specific for the heterologous antigen while including deletions in one or more genes essential or augmenting for CMV replication, dissemination or spread.

Methods of inducing a CD8+ T cell response to a heterologous antigen in which at least 10% of the CD8+ T cells are MHC-E restricted are disclosed. The method involves immunizing with a CMV vector that does not express UL128 and UL130 proteins. Also disclosed are recombinant CMV vectors comprising nucleic acids encoding a heterologous protein antigen, a UL40 protein, and a US28 protein but that do not express an active UL128 and UL130 protein. Also disclosed are recombinant CMV vectors comprising nucleic acids encoding a heterologous protein antigen, but that do not express an active UL40 protein, UL128 protein, UL130 protein, and optionally a US28 protein. Also disclosed are recombinant CMV vectors comprising nucleic acids encoding a heterologous protein antigen, but that do not express an active US28 protein, UL128 protein, UL130 protein, and optionally a UL40 protein.

This invention also relates to recombinant vectors expressing one or more of the human CMV (HCMV) glycoproteins US2, US3, US6 and US11 or corresponding functional rhesus CMV (RhCMV) homologues Rh182, Rh184, Rh185 or Rh189, methods of making them, uses for them, expression products from them, and uses for the expression products. This invention also relates to recombinant cytomegalovirus vectors vectors lacking one or more of the glycoproteins, methods of making them, uses for them, expression products from them, and uses for the expression products.

Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.

Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.