Formulation of the Rabies Virus Vaccine Vector Against Emerging Viruses
The inactivated rabies vaccine has been safely administered for decades. An immunogenic inactivated vaccine, non-replicating rabies virus rapidly activates an antibody response against the native glycoprotein. The boost response to rabies vaccination is especially robust, significantly increasing antibody titers. Recombinant rabies virus, attenuated to abolish neurovirulence when replication competent, has served as an immunogenic vaccine vector against emerging pathogens. Insertion of a foreign glycoprotein gene into the rabies virus genome expresses the recombinant protein on the surface of the virion. This strategy has been employed for nearly 20 emerging pathogens over the past decade. The most advanced and well-characterized rabies-vectored vaccines are for Ebola virus and SARS-CoV-2. For both vaccines, the immune response against the foreign antigen is significant and effective at protecting against viral challenge. Successful vaccine response to the rabies-based Ebola vaccine FILORAB1 and the SARSCoV-2 vaccine CORAVAX is noteworthy. However, responses are augmented by vaccine adjuvant toll-like receptor 4 agonists and/or inflammasome activation by a squalene oil-in-water emulsion. These adjuvants rapidly activate the innate immune system leading to a higher adaptive immune response. They also skew the response toward the type 1 helper T cell module of the immune system best suited for antiviral capability. Regardless of adjuvant formulation, the immune response to rabies vaccination is long-lived. 1 year post-immunization in mice, serum antibody titers against both rabies and the foreign glycoprotein are impressive. Antibody-secreting cells are present in the spleen and bone marrow of both FILORAB1 and CORAVAX immunized mice. Of note, lowering the standard dose of the vaccination increases these long-term effects as well as post-boost antibody titers in mice vaccinated with FILORAB1, but not CORAVAX.
Yankowski, Catherine, "Formulation of the Rabies Virus Vaccine Vector Against Emerging Viruses" (2023). ProQuest ETD Collection - Thomas Jefferson University. AAI30567518.