Expressed Antigens of Hantaviruses as Potential Vaccines for Hemorrhagic Fever with Renal Syndrome

Abstract

Hantaan (HTN) and related viruses, members of the genus Hantavirus, family Bunyaviridae (Schmaljohn and Dalrymple, 1983), cause clinically similar human diseases collectively termed hemorrhagic fever with renal syndrome (HFRS) (WHO, 1983). At least three distinct hantaviruses cause human disease: HTN virus, cause of Korean hemorrhagic fever in Korea and epidemic hemorrhagic fever elsewhere in Asia; Puumala (PUU) virus, cause of nephropathia epidemica, found in Europe west of the Ural mountains; and Seoul (SEO) virus, cause of a moderately severe form of HFRS, potentially found wherever urban rat populations are abundant (McKee et al., 1985). Hantaviruses are maintained in nature by chronically infected rodents, which shed infectious virus into the environment in urine, feces, and saliva (Lee et al., 1985; McKee et al 1985). Transmission to humans is usually by the aerosol route; and disease is characterized by an abrupt onset of fever, accompanied by varying degrees of kidney involvement and hemorrhagic manifestations, which may lead to shock, and death (McKee et al., 1983). A number of traditional, inactivated vaccines have been developed and tested in humans, including a rodent brain-derived vaccine developed in South Korea (Lee et al., 1990), and cell culture-derived vaccines, developed in China (Song et al., 1991; 1992). However, these vaccines have not been widely used, partly due to manufacturing difficulties associated with the slow and low-titered replication of hantaviruses in cell culture, and also because of the need to inactivate viral infectivity, which can lead to a loss of antigenic sites required for elicitation of a neutralizing antibody response. Instead of a traditional approach, we decided to pursue a molecular approach to HFRS vaccine development, by using eukaryotic virus vectors to express the genes of HTN virus. This report summarizes our studies with baculovirus- and vaccinia virus-expressed HTN proteins, and our attempts to develop and evaluate through pre-clinical tests a vaccinia-vectored vaccine for HFRS.