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

Abstract

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.

Vaccine Advances against Venezuelan, Eastern, and Western Equine Encephalitis Viruses

“…Coverage of potential linear epitopes was advanced as a method to compare candidate immunogens against such highly variable pathogens as HIV-1 [ 127 , 131 , 132 , 133 , 134 , 135 ], HCV [ 136 , 137 ], and Filoviridae [ 138 , 139 , 140 ]. The approach is motivated by the high density of experimentally confirmed epitopes throughout viral proteomes, extreme diversity of known HLA alleles, and the regional variation in dominant viral strains.…”

Pathogen Dose in Animal Models of Hemorrhagic Fever Virus Infections and the Potential Impact on Studies of the Immune Response

“…A limitation of mouse models of filovirus infections is that they generally require intraperitoneal (IP) infections, a route that leads to rapid dissemination of virus, but one that is not relevant to natural infection with these viruses, which are typically contracted via mucosal surfaces or breaches in the skin coming into contact with virus in contaminated bodily fluids [ 64 ]. Pre-clinical studies in mouse models using mouse-adapted viruses have been used for a variety of vaccines and treatments for EBOV and MARV, and have led to important observations and discoveries, including in the use of the VSV-EBOV vaccine and monoclonal antibodies for treatment of Ebola virus disease [ 65 , 66 , 67 , 68 ]. Due to the need for adaptation of viruses to mice, immunocompromised mice, such as those deficient in the interferon alpha/beta receptor (IFNAR-/-), interferon alpha/beta/gamma (IFN-α/βγR-/-) receptors, or signal transducer and activator of transcription 1 (STAT1) have been used as models for filovirus infection [ 69 , 70 ].…”

Epigraph Hemagglutinin Vaccine Induces Broad Cross-reactive Immunity Against Swine H3 Influenza Virus

“…Epigraph is a graph-based algorithm that creates a cocktail of vaccine antigens designed to maximize the potential epitope coverage of a highly diverse population. This epigraph algorithm has been used to predict therapeutic HIV vaccine candidates 18 and has shown promising potential in vivo as a Pan-Filovirus vaccine 19 . Here, we utilize the Epigraph vaccine designer in the development of a universal swH3 vaccine by computationallydesigning a cocktail of three swH3 hemagglutinins (HA), a surface glycoprotein of influenza.…”