Preliminary human trial of inactivated golden hamster kidney cell (GHKC) vaccine against haemorrhagic fever with renal syndrome (HFRS).

An inactivated golden hamster kidney cell culture (GHKC) vaccine against haemorrhagic fever with renal syndrome (HFRS) has been developed in recent years. A monovalent GHKC vaccine (lot 88-17) was prepared with L99 strain of the rat-type hantavirus, adapted in suckling mouse brain, cultivated in GHKC, and inactivated with 0.025% formalin, and a preliminary trial of the vaccine was carried out in a small number of human volunteers with the approval of the Ministry of Public Health, PRC, in order to identify safety and antibody response of the vaccine. Three inoculations were made on days 0, 7 and 28 respectively, by the intramuscular route with 1 ml vaccine each time for every volunteer. No obvious side effect was observed in vaccinees within 3 days after each inoculation. All 12 vaccinees (10 received three inoculations, and two received two inoculations of the vaccine) showed positive seroconversion of IgG antibody (by IFAT and ELISA) and neutralizing antibody (by enzyme focus reduction neutralization test, EFRNT), and 10 of them were still seropositive 180 and 360 days after the first inoculation. These results suggest that this vaccine would be safe for human use, and could effectively induce IgG and neutralizing antibody responses.

Morphology and morphogenesis of viruses of hemorrhagic fever with renal syndrome (HFRS). I. Some peculiar aspects of the morphogenesis of various strains of HFRS virus.

The morphology and morphogenesis of viruses of hemorrhagic fever with renal syndrome (HFRS) were studied by thin-section electron microscopy. Ten strains of HFRS virus isolated in China and one strain isolated in Korea were compared. The virions varied in size as well as in the shape and character of their inner components. Both intracellular and extracellular ribosome-like, electron-dense, virus-associated granules were seen. A viral antigen layer was often visualized on the surface of HFRS virus-infected cells, as confirmed by immune electron microscopy. Aberrant tailed particles and elongated rod-like particles were seen infrequently. The morphogenesis of HFRS viruses appears to be more complex than that of other members of the family Bunyaviridae. The prototype Hantaan virus shares a common morphology and morphogenesis with the other HFRS viruses studied.

Antigenic difference between viral strains causing classical and mild types of epidemic hemorrhagic fever with renal syndrome in China.

The antigenic relationship between viral isolates from Apodemus and Rattus that appear to cause the classical and mild types of epidemic hemorrhagic fever (EHF) in China was studied by cross-immunofluorescence, cross-neutralization, immunofluorescence blocking tests, and cross-enzyme-linked immunosorbent assay (ELISA). Obvious antigenic diversity between the isolates was demonstrated by cross-neutralization, immunofluorescence blocking tests, and cross-ELISA. Antisera from patients with classical EHF neutralized viruses of both types to a similar degree, but antisera from patients with mild EHF showed little neutralization of apodemus virus. Similarly, antisera from classical EHF blocked immunofluorescence by monoclonal antibody (25-1 McAb) derived from apodemus virus to both viral antigens, but antisera from mild EHF gave only low-grade blocking against apodemus viral antigen. Direct antigenic titrations of both viral strains by cross-ELISA yielded similar results. That distinct antigenic differences exist between viral strains causing these two types of EHF might be of great importance to the serological differentiation of the viruses and the study of EHF vaccine.

Etiologic studies of epidemic hemorrhagic fever (hemorrhagic fever with renal syndrome).

Two strains of epidemic hemorrhagic fever (EHF) virus were isolated from the lung tissues of Apodemus agrarius mice that were captured in an area where EHF is endemic. The strains were isolated by passages in A. agrarius mice from a nonendemic area. Identification of the isolates by usual procedures was confirmed by repeated blind tests with coded sera. Contamination with certain known viruses such as reovirus, adenovirus (types 3 and 7), and other pathogens, such as murine typhus rickettsiae and Leptospira, which may be naturally present in wild rodents, appeared to have been ruled out. The antigen slides made from these isolates are in use in the specific diagnosis and seroepidemiologic studies of EHF. The first successful application is the serodiagnosis of a mild type of hemorrhagic fever that occurs with characteristic epidemiologic features in certain provinces of China.

Morphological evidence for identifying the viruses of hemorrhagic fever with renal syndrome as candidate members of the Bunyaviridae family. Brief report.

Thin section immuno-electron microscopy has been successfully applied to investigate and identify the classical and mild form of HFRS viruses isolated in the People's Republic of China. The results showed that all the 8 strains studied (derived from different parts of China, adapted in different cell lines) share a common morphology and morphogenesis. Essentially, the viruses possess characteristics of members of the Bunyaviridae Family, however, differing by a larger size and size variation and formation of cytoplasmic viral inclusions.