Advancement of a cost-effective MVA-based Hantavirus vaccine (HantaVacc).

   Seoul virus (SEOV) and Hantaan virus (HTNV) are widespread pathogens maintained in rodents and transmitted to humans in aerosols of rodent excreta. Human infection results in Haemorrhagic Fever with Renal Syndrome (HFRS), a key burden of disease in many low and middle income countries with between 100,000-150,000 cases documented worldwide per year. Whilst other Hantaviruses exist, they cause more infrequent types of disease or are geographically restricted to the Americas, the need for vaccine intervention against them is less urgent than for SEOV and HTNV.      During the 12 month Stream 1 funded project, we developed a multi-valent vaccine, termed MVA-HantaVacc, based on the vector Modified Vaccinia Ankara (MVA) containing a recombinant mosaic nucleoprotein  of SEOV and HTNV. MVA-based vaccines are efficient and cost-effective; they offer many advantages including a proven safety record, the ability to elicit both cellular and humoral immunity, thermostability and ease of manufacture. We then demonstrated that MVA-HantaVacc is immunogenic in mice. A strong antigen-specific recall T-cell response was observed along with production of Hantavirus-specific antibodies. In the absence of a suitable laboratory disease model of SEOV or HTNV infection, vaccine efficacy was assessed in type-I interferon receptor knockout mice (strain A129) which can be experimentally infected with SEOV. Animals immunised with MVA-HantaVacc demonstrated clearance of virus from key tissues in contrast to control groups. This is the first demonstration of a successful research grade MVA Hantavirus vaccine.       In order to further progress MVA-HantaVacc through a Phase I human clinical trial, we will first re-engineer the Hantavirus nucleoprotein antigens into a GMP-compliant MVA vector. We will then demonstrate bioequivalence of the new vaccine with the 'research grade' vaccine, before manufacturing  a GMP batch which will undergo stringent quality control and toxicity testing. Once complete, MVA-HantaVacc will enter into a Phase I clinical trial to test safety and immunogenicity in healthy human volunteers. We have already started discussi