A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS)

Abstract

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.

Knowledge, attitudes, and practices regarding hantavirus disease and acceptance of a vaccine trial in rural communities of southern Chile

“…15 A candidate ANDV vaccine is likely to be available for use in human trials in the near future. [16][17][18][19] A Hantaan virus (HTNV) inactivated vaccine has been in use in China since 1990. DNA vaccines carrying plasmids with M segments from pathogenic New and Old World hantaviruses are in development.…”

Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges

“…For both the hantavirus and VEEV DNA vaccines, gene optimization was found to increase expression and to improve antibody responses in animals and humans. 28,[30][31][32][33][34][35] For the 2 hantavirus vaccines, optimization also mitigated immune interference, which we observed when using non-optimized constructs. 27,29 Although we did not have nonoptimized constructs for the SUDV or RAVV DNA vaccines, we Figure 6.…”

Effects of Anthropogenic Events and Viral Persistence on Rodent Reservoirs of Hantavirus Infection: Understanding Host-Pathogen Interactions Facilitates Novel Approaches to Intervention Strategies

“…One approach is to prepare a single vaccine that would protect against multiple pathogenic hantavirus species. A recent study shows that a combination of plasmids from four pathogenic hantavirus species, HTNV, PUUV, Andes virus (ANDV) and Sin Nombre virus (SNV), could elicit comparable levels of neutralizing antibody against each species [130]. A combination of either HTNV and PUUV or ANDV and SNV provided only partial success.…”