Controlled viral glycoprotein expression as a safety feature in a bivalent rabies-ebola vaccine.
Using a recombinant rabies (RABV) vaccine platform, we have developed several safe and effective vaccines. Most recently, we have developed a RABV-based ebolavirus (EBOV) vaccine that is efficacious in nonhuman primates. One safety feature of this vaccine is the utilization of a live but replication-deficient RABV construct. In this construct, the RABV glycoprotein (G) has been deleted from the genome, requiring G trans complementation in order for new infectious viruses to be released from the initial infected cell. Here we analyze this safety feature of the bivalent RABV-based EBOV vaccine comprised of the G-deleted RABV backbone expressing EBOV glycoprotein (GP). We found that, while the level of RABV genome in infected cells is equivalent regardless of G supplementation, the production of infectious virus is indeed restricted by the lack of G, and most importantly, that the presence of EBOV GP does not substitute for G. These findings further support the safety profile of this replication-deficient RABV-EBOV bivalent vaccine.
['Papaneri|Amy B|AB|', 'Bernbaum|John G|JG|', 'Blaney|Joseph E|JE|', 'Jahrling|Peter B|PB|', 'Schnell|Matthias J|MJ|', 'Johnson|Reed F|RF|']
D000818:Animals D000956:Antigens, Viral D046129:Ebola Vaccines D017353:Gene Deletion D015870:Gene Expression D005816:Genetic Complementation Test D006023:Glycoproteins D019142:Hemorrhagic Fever, Ebola D011323:Primates D011818:Rabies D011819:Rabies Vaccines D011994:Recombinant Proteins D014613:Vaccines, Attenuated D014614:Vaccines, Synthetic D014759:Viral Envelope Proteins
Vaccine Biodefense Ebola Filovirus RNA viruses Rabies virus