Sin Nombre virus (SNV; family Bunyaviridae, genus Hantavirus) causes a hemorrhagic
fever known as
hantavirus pulmonary syndrome (HPS) in North America. There have been approximately 200 fatal cases of HPS in the United States since 1993, predominantly in healthy working-age males (case fatality rate 35%). There are no FDA-approved
vaccines or drugs to prevent or treat HPS. Previously, we reported that hantavirus
vaccines based on the full-length M gene segment of Andes virus (ANDV) for HPS in South America, and Hantaan virus (HTNV) and Puumala virus (PUUV) for
hemorrhagic fever with renal syndrome (
HFRS) in Eurasia, all elicited high-titer
neutralizing antibodies in animal models.
HFRS is more prevalent than HPS (>20,000 cases per year) but less pathogenic (case fatality rate 1-15%). Here, we report the construction and testing of a SNV full-length M gene-based
DNA vaccine to prevent HPS. Rabbits vaccinated with the SNV
DNA vaccine by muscle electroporation (mEP) developed high titers of
neutralizing antibodies. Furthermore, hamsters vaccinated three times with the SNV
DNA vaccine using a gene gun were completely protected against SNV
infection. This is the first
vaccine of any kind that specifically elicits high-titer
neutralizing antibodies against SNV. To test the possibility of producing a pan-hantavirus
vaccine, rabbits were vaccinated by mEP with an HPS mix (ANDV and SNV plasmids), or
HFRS mix (HTNV and PUUV plasmids), or HPS/
HFRS mix (all four plasmids). The HPS mix and
HFRS mix elicited
neutralizing antibodies predominantly against ANDV/SNV and HTNV/PUUV, respectively. Furthermore, the HPS/
HFRS mix elicited
neutralizing antibodies against all four viruses. These findings demonstrate a pan-hantavirus
vaccine using a mixed-plasmid
DNA vaccine approach is feasible and warrants further development.