Preparation of candidate vaccinia-vectored vaccines for haemorrhagic fever with renal syndrome.

Two vaccinia-vectored candidate vaccines for haemorrhagic fever with renal syndrome were prepared by inserting cDNA, representing the medium (M) genome segment, or the M and the small (S) genome segments of Hantaan virus into the thymidine kinase gene of the Connaught vaccine strain of vaccinia virus. In the single recombinant, the M segment was placed under control of the vaccinia virus 7.5 kDa promoter. In the double recombinant, the M and S segments were placed under control of the vaccinia virus 7.5 kDa and 11 kDa promoters, respectively. An immunoplaque assay technique was developed to select recombinants without the need for expression of irrelevant genes or use of potential mutagens. Proteins indistinguishable from authentic viral envelope glycoproteins and nucleocapsid protein were observed by immunoprecipitation with antibodies to Hantaan virus. The recombinant expressing both the M and the S segments was selected for further development and testing as a human vaccine.