Complete protection of the BALB/c and C57BL/6J mice against Ebola and Marburg virus lethal challenges by pan-filovirus T-cell epigraph vaccine.

There are a number of vaccine candidates under development against a small number of the most common outbreak filoviruses all employing the virus glycoprotein (GP) as the vaccine immunogen. However, antibodies induced by such GP vaccines are typically autologous and limited to the other members of the same species. In contrast, T-cell vaccines offer a possibility to design a single pan-filovirus vaccine protecting against all known and even likely existing, but as yet unencountered members of the family. Here, we used a cross-filovirus immunogen based on conserved regions of the filovirus nucleoprotein, matrix and polymerase to construct simian adenovirus- and poxvirus MVA-vectored vaccines, and in a proof-of-concept study demonstrated a protection of the BALB/c and C57BL/6J mice against high, lethal challenges with Ebola and Marburg viruses, two distant members of the family, by vaccine-elicited T cells in the absence of GP antibodies. Author summary Development of an effective vaccine against filovirus outbreaks is an important public health aim. Here, we demonstrate the principle that cellular responses can not only protect two strains of mice against a high lethal virus challenge of 1000 LD50 in the absence of glycoprotein antibodies, but a single epigraph T-cell vaccine can do so against distant members of the filovirus family, EBOV and MARV. This suggests a possibility that this candidate vaccine also protects against other known as well as yet unencountered viruses of the filovirus family; it is a pan-filovirus vaccine.