Vaccines against hemorrhagic fever with renal syndrome

Hantaan virus (HTNV) and Puumala virus (PUUV) are major etiological agents of hemorraghic fever With renal syndrome (HFRS) on the Eurasian continent. A formalin-inactivated HTNV vaccine (Hantavax(TM), KGC) has been available since 1990 in Korea. Hantavax contains 5 mu g of protein, < 0.01 ng of myelin basic protein and 5,120 U enzyme-linked immunosorbent assay (ELISA) of virus antigen in 0.5 mL. Seroconversion rates of vaccinees were 52%, 96% and 63% by immunofluorescence antibody (IFA), and 25%, 75% and 16% by plaque-reduction neutralization test (PRNT) after 1, 3 and 12 months, respectively, after the first vaccination. After booster vaccination at 1 year, vaccinees maintained high levels of antibodies for at least 2 years, Newly developed PUUV vaccine contains 6 mu g of total protein, < 0.01 ng of myelin basic protein and 5,120 U/ELISA of antigen in 0.5 mL. HTNV-PUUV combination vaccine contains both 5,120 U of HTN and PUU antigen in 1.0 mL. Mean IFAb titers of hamsters vaccinated with combination vaccine were 687, 568, 550, 516 and 431, and mean NAb titers were 711. 42, 24, 410 and 1.6 against HTNV, Seoul (SEOV), Belgrada/Dobrava (BEL/DOBV), PUUV, Sin Nombre (SNV) and New York (NYV) viruses, respectively. By nested reverse transcriptase-polymerase chain reaction, vaccinated hamsters challenged with HTNV, SEOV, BEL/DOBV or PUUV were neither viremic nor had detectable virus in their lungs. By contrast, SNV- or NYV-challenged hamsters were viremic and had virus in their lungs. NAb titers of 12 vaccinees ranged from 10 to 1,280 against HTNV and from 10 to 640 against PUUV.