Immunogenicity of a trivalent haemorrhagic fever vaccine candidate against Sudan virus, Marburg virus and Lassa virus in an mpox vaccine.

A multivalent vaccine targeting high-consequence infectious diseases in Sub-Saharan Africa (SSA), which are linked to high mortality, morbidity and overlapping clinical manifestations, would significantly improve health security and economic stability in this region. Trivalent vector vaccines were devised to deliver digitally optimized versions of Orthoebolavirus, Orthomarburgvirus glycoproteins (GPs) and a Lassa mammarenavirus (LASV) nucleoprotein (NP) by a single Modified Vaccinia Ankara (MVA) known to protect against mpox virus (MPXV) along with a matched DNA vaccine. Three immunizations in mice and Hartley guinea pigs with MVA only or a DNA prime followed by two MVA administrations induced comparable levels of binding antibodies and LASV-specific T-cells, respectively. While DNA priming mitigated MVA-specific antibody responses, GP- and NP-specific antibodies developed already after a single MVA vaccination. Although a post-outbreak Ebola virus vaccine is available, outbreaks by other filoviruses, annual LASV epidemics and increased incidence of MPXV infections support the rationale for an MVA-based trivalent haemorrhagic fever vaccine for endemic and high-risk human populations in SSA.