Multivalent Vaccines for Rabies Virus and Filoviruses

No vaccine candidates against Ebola virus (EBOV) or Marburg virus (MARV) are nearing licensure and the need to develop a safe and efficacious vaccine against filoviruses continues. Whereas several preclinical vaccine candidates against EBOV or MARV exist, their further development is a major challenge based on safety concerns, pre-existing vector immunity, and issues such as manufacturing, dosage, and marketability. The inventors have developed a new platform based on live or chemically inactivated (killed) rabies virus (RABV) virions containing EBOV glycoprotein (GP) in their envelope. In preclinical trials, immunization with such recombinant RABV virions provided excellent protection in mice against lethal challenge with the mouse adapted EBOV and RABV. More specifically, the inventors have developed a trivalent filovirus vaccine based on killed rabies virus virions for use in humans to confer protection from all medically relevant filoviruses and RABV. Two additional vectors containing EBOV Sudan GP or MARV GP are planned to be constructed in addition to the previously developed EBOV Zaire GP containing vaccine. The efficiency of these vaccines against challenge with EBOV, MARV and RABV will be studied in multiple preclinical studies. Live attenuated vaccines are being developed for use in at risk nonhuman primate populations in Africa and inactivated vaccines are being developed for use in humans.