Polyclonal alpaca antibodies protect against hantavirus pulmonary syndrome in a lethal Syrian hamster model.

The use of antibody-based therapies for the treatment of high consequence viral pathogens has gained interest over the last fifteen years. Here, we sought to evaluate the use of unique camelid-based IgG antibodies to prevent lethal hantavirus pulmonary syndrome (HPS) in Syrian hamsters. Using purified, polyclonal IgG antibodies generated in DNA-immunized alpacas, we demonstrate that post-exposure treatments reduced viral burdens and organ-specific pathology associated with lethal HPS. Antibody treated animals did not exhibit signs of disease and were completely protected. The unique structures and properties, particularly the reduced size, distinct paratope formation and increased solubility of camelid antibodies, in combination with this study support further pre-clinical evaluation of heavy-chain only antibodies for treatment of severe respiratory diseases, including HPS.

The 1993 Hantavirus Pulmonary Syndrome Outbreak and Lessons for Today.

While grappling with the implications of the current COVID-19 pandemic, we have perhaps overlooked recent history dealing with previous outbreaks. In the spring of 1993, America was presented with an outbreak of Hantavirus Pulmonary Syndrome caused by the Sin Nombre virus. This article recounts the investigation into this disease and discusses the spectrum of issues that medical communities must face as it deals with a mysterious outbreak.

Oral Vaccination With Recombinant Vesicular Stomatitis Virus Expressing Sin Nombre Virus Glycoprotein Prevents Sin Nombre Virus Transmission in Deer Mice.

Sin Nombre virus (SNV) is the major cause of hantavirus cardiopulmonary syndrome (HCPS) in North America, a severe respiratory disease with a high fatality rate. SNV is carried by Peromyscus maniculatus, or deer mice, and human infection occurs following inhalation of aerosolized virus in mouse excreta or secreta, often in peri-domestic settings. Currently there are no FDA approved vaccines or therapeutics for SNV or any other hantaviruses, therefore prevention of infection is an important means of reducing the disease burden of HCPS. One approach for preventing HCPS cases is to prevent the spread of the virus amongst the rodent reservoir population through bait vaccination. However, bait style vaccines for rodent-borne viruses have not been employed in the field, unlike those targeting larger species. Here we utilized a recombinant vesicular stomatitis virus expressing SNV glycoprotein precursor (rVSVΔG/SNVGPC) in an attempt to prevent SNV transmission. Vaccination of deer mice with rVSVΔG/SNVGPC was able to reduce viral RNA copy numbers in the blood and lungs of directly infected animals. More importantly, vaccination, either intramuscularly or orally, significantly reduced the number of transmission events in a SNV transmission model compared with control animals. This provides a proof-of-concept in which oral vaccination of deer mice results in protection against acquiring the virus following direct contact with infected deer mice. Further development of bait style vaccines for SNV or other rodent-borne viruses could provide an effective means of reducing disease burden.

Spatiotemporal Dynamics of Hantavirus Cardiopulmonary Syndrome Transmission Risk in Brazil.

BACKGROUND: Hantavirus disease in humans is rare but frequently lethal in the Neotropics. Several abundant and widely distributed Sigmodontinae rodents are the primary hosts of Orthohantavirus and, in combination with other factors, these rodents can shape hantavirus disease. Here, we assessed the influence of host diversity, climate, social vulnerability and land use change on the risk of hantavirus disease in Brazil over 24 years. METHODS: Landscape variables (native forest, forestry, sugarcane, maize and pasture), climate (temperature and precipitation), and host biodiversity (derived through niche models) were used in spatiotemporal models, using the 5570 Brazilian municipalities as units of analysis. RESULTS: Amounts of native forest and sugarcane, combined with temperature, were the most important factors influencing the increase of disease risk. Population at risk (rural workers) and rodent host diversity also had a positive effect on disease risk. CONCLUSIONS: Land use change-especially the conversion of native areas to sugarcane fields-can have a significant impact on hantavirus disease risk, likely by promoting the interaction between the people and the infected rodents. Our results demonstrate the importance of understanding the interactions between landscape change, rodent diversity, and hantavirus disease incidence, and suggest that land use policy should consider disease risk. Meanwhile, our risk map can be used to help allocate preventive measures to avoid disease.

Vesicular Stomatitis Virus-Based Vaccines Provide Cross-Protection against Andes and Sin Nombre Viruses.

Andes virus (ANDV) and Sin Nombre virus (SNV) are the main causative agents responsible for hantavirus cardiopulmonary syndrome (HCPS) in the Americas. HCPS is a severe respiratory disease with a high fatality rate for which there are no approved therapeutics or vaccines available. Some vaccine approaches for HCPS have been tested in preclinical models, but none have been tested in infectious models in regard to their ability to protect against multiple species of HCPS-causing viruses. Here, we utilize recombinant vesicular stomatitis virus-based (VSV) vaccines for Andes virus (ANDV) and Sin Nombre virus (SNV) and assess their ability to provide cross-protection in infectious challenge models. We show that, while both rVSVΔG/ANDVGPC and rVSVΔG/SNVGPC display attenuated growth as compared to wild type VSV, each vaccine is able to induce a cross-reactive antibody response. Both vaccines protected against both homologous and heterologous challenge with ANDV and SNV and prevented HCPS in a lethal ANDV challenge model. This study provides evidence that the development of a single vaccine against HCPS-causing hantaviruses could provide protection against multiple agents.

Evaluation of habitat requirements of small rodents and effectiveness of an ecologically-based management in a hantavirus-endemic natural protected area in Argentina.

Hantavirus pulmonary syndrome is a severe cardio pulmonary disease transmitted to humans by sylvan rodents found in natural and rural environments. Disease transmission is closely linked to the ecology of animal reservoirs and abiotic factors such as habitat characteristics, season or climatic conditions. The main goals of this research were: to determine the biotic and abiotic factors affecting richness and abundance of rodent species at different spatial scales, to evaluate different methodologies for studying population of small rodents, and to describe and analyze an ecologically-based rodent management experience in a highly touristic area. A 4-year study of small rodent ecology was conducted between April 2007 and August 2011 in the most relevant habitats of El Palmar National Park, Argentina. Management involved a wide range of control and prevention measures, including poisoning, culling and habitat modification. A total of 172 individuals of 5 species were captured with a trapping effort of 13 860 traps-nights (1.24 individuals/100 traps-nights). Five rodent species were captured, including 2 hantavirus-host species, Oligoryzomys nigripes and Akodon azarae. Oligoryzomys nigripes, host of a hantavirus that is pathogenic in humans, was the most abundant species and the only one found in all the studied habitats. Our results are inconsistent with the dilution effect hypothesis. The present study demonstrates that sylvan rodent species, including the hantavirus-host species, have distinct local habitat selection and temporal variation patterns in abundance, which may influence the risk of human exposure to hantavirus and may have practical implications for disease transmission as well as for reservoir management.

Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure.

Andes virus (ANDV) and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS) cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgYΔFc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA) for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA80 titers >100,000). Analysis of IgY and IgYΔFc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. α-ANDV immune sera, or IgY/IgYΔFc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50). Both immune sera, and egg-derived purified IgY/IgYΔFc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgYΔFc purified from normal geese (n=8), or no-treatment (n=8), developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral biological product capable of preventing a lethal disease when administered post-exposure.

Assessing prevention measures and Sin Nombre hantavirus seroprevalence among workers at Yosemite National Park.

BACKGROUND: During 2012, a total of 10 overnight visitors to Yosemite National Park (Yosemite) became infected with a hantavirus (Sin Nombre virus [SNV]); three died. SNV infections have been identified among persons with occupational exposure to deer mice (Peromyscus maniculatus). METHODS: We assessed SNV infection prevalence, work and living environments, mice exposures, and SNV prevention training, knowledge, and practices among workers of two major employers at Yosemite during September-October, 2012 by voluntary blood testing and a questionnaire. RESULTS: One of 526 participants had evidence of previous SNV infection. Participants reported frequently observing rodent infestations at work and home and not always following prescribed safety practices for tasks, including infestation cleanup. CONCLUSION: Although participants had multiple exposures to deer mice, we did not find evidence of widespread SNV infections. Nevertheless, employees working around deer mice should receive appropriate training and consistently follow prevention policies for high-risk activities.

DNA vaccine-derived human IgG produced in transchromosomal bovines protect in lethal models of hantavirus pulmonary syndrome.

Polyclonal immunoglobulin-based medical products have been used successfully to treat diseases caused by viruses for more than a century. We demonstrate the use of DNA vaccine technology and transchromosomal bovines (TcBs) to produce fully human polyclonal immunoglobulins (IgG) with potent antiviral neutralizing activity. Specifically, two hantavirus DNA vaccines [Andes virus (ANDV) DNA vaccine and Sin Nombre virus (SNV) DNA vaccine] were used to produce a candidate immunoglobulin product for the prevention and treatment of hantavirus pulmonary syndrome (HPS). A needle-free jet injection device was used to vaccinate TcB, and high-titer neutralizing antibodies (titers >1000) against both viruses were produced within 1 month. Plasma collected at day 10 after the fourth vaccination was used to produce purified α-HPS TcB human IgG. Treatment with 20,000 neutralizing antibody units (NAU)/kg starting 5 days after challenge with ANDV protected seven of eight animals, whereas zero of eight animals treated with the same dose of normal TcB human IgG survived. Likewise, treatment with 20,000 NAU/kg starting 5 days after challenge with SNV protected immunocompromised hamsters from lethal HPS, protecting five of eight animals. Our findings that the α-HPS TcB human IgG is capable of protecting in animal models of lethal HPS when administered after exposure provides proof of concept that this approach can be used to develop candidate next-generation polyclonal immunoglobulin-based medical products without the need for human donors, despeciation protocols, or inactivated/attenuated vaccine antigen.

[Conditions for the transmission of Hantavirus in Rio Negro, Argentina]. / Condiciones para la transmision del hantavirus en zona andina de Río Negro, Argentina.

Hantavirus Pulmonary Syndrome (HPS) is a disease of viral etiology that affects humans causing severe acute respiratory symptoms. In Patagonia the disease is caused by the Andes Virus (AND) and transmitted by the rodent Oligoryzomys longicaudatus. The aim of this study was to identify those human activities that increase the risk of exposure to rodents, what we call "contagious scenarios". A retrospective study was performed with data obtained from cases in Rio Negro, which included clinic-epidemiological records and ecological/environmental assessment reports. The following variables were considered: age, sex, season, percentage of urbanization, geographic location, human settlements in rodent infested areas, probable source of exposure, type of activity and level of sanitary development. In total 32 cases were studied. Exposure was verified in 18 (56.2 %) cases in rural areas and 10 cases (31.3%) in small rural towns. In relation to anthropogenic environment, 24 (75%) cases were reported in developed settlements and 8 cases (25%) were related to slightly modified areas. Major exposition in El Bolson identified 8 cases of indoor activities of the total 18 reported in the area (44.5%), while in Bariloche 8 (57.1%) cases out of 14 were reported in outdoor surroundings. In general, activities that generated greater risk were work-related, accounting for 23 (71.9%) cases while 7 were related to recreational activities (28.1%). The identification of "contagious scenarios" at local level provided information for an effective application of available resources in terms of prevention and sanitary education.

Condiciones para la transmision del hantavirus en zona andina de Río negro, Argentina

El Síndrome Pulmonar por Hantavirus (SPH) es una enfermedad de etiología viral que causa en el hombre un cuadro respiratorio grave. En Patagonia, la enfermedad es causada por el virus Andes Sur (AND), transmitido por el roedor Oligoryzomys longicaudatus. El objetivo del presente trabajo fue identificar las actividades del hombre que favorecen su exposición a roedores, denominados escenarios de contagio. Se realizó un estudio retrospectivo a partir de información recolectada en investigaciones de casos ocurridos en Río Negro, mediante Fichas Clínico-Epidemiológicas e informes de evaluación ecológico/ambiental. Se definieron como variables a ser consideradas: edad, sexo, época del año, grado de urbanización, localización geográfica, integración del hombre al hábitat de roedores, fuente probable de exposición, actividad humana y nivel de saneamiento. Se estudiaron 32 casos. La exposición rural se verificó en 18 (56.2%) de los casos y 10 (31.3%) en paraje rural (grupo de viviendas en zona rural). En relación al ambiente antropogénico 24 (75%) resultaron en ambientes modificados por el hombre y 8 (25%) en áreas poco modificadas. El sitio de exposición de mayor importancia en El Bolsón fue el interior de edificaciones en 8 de los 18 casos allí registrados (44.5%), mientras que en Bariloche fueron ambientes de exterior con 8/14 (57.1%) casos. La actividad de riesgo fue laboral en 23 (71.9%) de los casos y recreacional en 7 (28.1%). Determinar los escenarios de contagio a nivel local ha aportado información para aplicar todos los recursos disponibles en materia de prevención y educación sanitaria.

Hantavirus Pulmonary Syndrome (HPS) is a disease of viral etiology that affects humans causing severe acute respiratory symptoms. In Patagonia the disease is caused by the Andes Virus (AND) and transmitted by the rodent Oligoryzomys longicaudatus. The aim of this study was to identify those human activities that increase the risk of exposure to rodents, what we call "contagious scenarios". A retrospective study was performed with data obtained from cases in Rio Negro, which included clinic-epidemiological records and ecological/environmental assessment reports. The following variables were considered: age, sex, season, percentage of urbanization, geographic location, human settlements in rodent infested areas, probable source of exposure, type of activity and level of sanitary development. In total 32 cases were studied. Exposure was verified in 18 (56.2 %) cases in rural areas and 10 cases (31.3%) in small rural towns. In relation to anthropogenic environment, 24 (75%) cases were reported in developed settlements and 8 cases (25%) were related to slightly modified areas. Major exposition in El Bolson identified 8 cases of indoor activities of the total 18 reported in the area (44.5%), while in Bariloche 8 (57.1%) cases out of 14 were reported in outdoor surroundings. In general, activities that generated greater risk were work-related, accounting for 23 (71.9%) cases while 7 were related to recreational activities (28.1%). The identification of "contagious scenarios" at local level provided information for an effective application of available resources in terms of prevention and sanitary education.

A hantavirus pulmonary syndrome (HPS) DNA vaccine delivered using a spring-powered jet injector elicits a potent neutralizing antibody response in rabbits and nonhuman primates.

Sin Nombre virus (SNV) and Andes virus (ANDV) cause most of the hantavirus pulmonary syndrome (HPS) cases in North and South America, respectively. The chances of a patient surviving HPS are only two in three. Previously, we demonstrated that SNV and ANDV DNA vaccines encoding the virus envelope glycoproteins elicit high-titer neutralizing antibodies in laboratory animals, and (for ANDV) in nonhuman primates (NHPs). In those studies, the vaccines were delivered by gene gun or muscle electroporation. Here, we tested whether a combined SNV/ANDV DNA vaccine (HPS DNA vaccine) could be delivered effectively using a disposable syringe jet injection (DSJI) system (PharmaJet, Inc). PharmaJet intramuscular (IM) and intradermal (ID) needle-free devices are FDA 510(k)-cleared, simple to use, and do not require electricity or pressurized gas. First, we tested the SNV DNA vaccine delivered by PharmaJet IM or ID devices in rabbits and NHPs. Both IM and ID devices produced high-titer anti-SNV neutralizing antibody responses in rabbits and NHPs. However, the ID device required at least two vaccinations in NHP to detect neutralizing antibodies in most animals, whereas all animals vaccinated once with the IM device seroconverted. Because the IM device was more effective in NHP, the Stratis(®) (PharmaJet IM device) was selected for follow-up studies. We evaluated the HPS DNA vaccine delivered using Stratis(®) and found that it produced high-titer anti-SNV and anti-ANDV neutralizing antibodies in rabbits (n=8/group) as measured by a classic plaque reduction neutralization test and a new pseudovirion neutralization assay. We were interested in determining if the differences between DSJI delivery (e.g., high-velocity liquid penetration through tissue) and other methods of vaccine injection, such as needle/syringe, might result in a more immunogenic DNA vaccine. To accomplish this, we compared the HPS DNA vaccine delivered by DSJI versus needle/syringe in NHPs (n=8/group). We found that both the anti-SNV and anti-ANDV neutralizing antibody titers were significantly higher (p-value 0.0115) in the DSJI-vaccinated groups than the needle/syringe group. For example, the anti-SNV and anti-ANDV PRNT50 geometric mean titers (GMTs) were 1,974 and 349 in the DSJI-vaccinated group versus 87 and 42 in the needle/syringe group. These data demonstrate, for the first time, that a spring-powered DSJI device is capable of effectively delivering a DNA vaccine to NHPs. Whether this HPS DNA vaccine, or any DNA vaccine, delivered by spring-powered DSJI will elicit a strong immune response in humans, requires clinical trials.

Twenty years of hantavirus pulmonary syndrome in Brazil: a review of epidemiological and clinical aspects.

Hantavirus infection is transmitted to humans by wild rodents and the most common clinical form in Brazil is the Hantavirus Pulmonary Syndrome (HPS). The first serological evidence of the disease was identified in 1990, in Recife, Pernambuco State, and later in 1993 in Juquitiba, State of São Paulo. Since then there has been a progressive increase in case notification in all regions of the country. The clinical aspects of the disease in Brazil are characterized by a prodromal phase, with nonspecific signs and symptoms of an acute febrile illness. After about three days, respiratory distress develops, accompanied by dry cough that turns progressively productive, evolving to dyspnea and respiratory failure with cardiogenic shock. Although the majority of patients receive hospital care in intensive care therapy units, case-fatality rate in Brazil ranges from 33% to 100% depending on the region. Besides it has to be added the problem of differential diagnosis with other prevalent diseases in the country, like dengue and leptospirosis. Questions about the impact of uncontrolled urbanization and other environmental changes caused by human action have been raised. Due to increasing incidence and high case-fatality, there is an urge to respond to such questions to recommend preventative measures. This article aims to review the main acquisitions in clinical and epidemiological knowledge about HPS in Brazil in the last twenty years.

Ribavirin protects Syrian hamsters against lethal hantavirus pulmonary syndrome--after intranasal exposure to Andes virus.

Andes virus, ANDV, harbored by wild rodents, causes the highly lethal hantavirus pulmonary syndrome (HPS) upon transmission to humans resulting in death in 30% to 50% of the cases. As there is no treatment for this disease, we systematically tested the efficacy of ribavirin in vitro and in an animal model. In vitro assays confirmed antiviral activity and determined that the most effective doses were 40 µg/mL and above. We tested three different concentrations of ribavirin for their capability to prevent HPS in the ANDV hamster model following an intranasal challenge. While the highest level of ribavirin (200 mg/kg) was toxic to the hamster, both the middle (100 mg/kg) and the lowest concentration (50 mg/kg) prevented HPS in hamsters without toxicity. Specifically, 8 of 8 hamsters survived intranasal challenge for both of those groups whereas 7 of 8 PBS control-treated animals developed lethal HPS. Further, we report that administration of ribavirin at 50 mg/kg/day starting on days 6, 8, 10, or 12 post-infection resulted in significant protection against HPS in all groups. Administration of ribavirin at 14 days post-infection also provided a significant level of protection against lethal HPS. These data provide in vivo evidence supporting the potential use of ribavirin as a post-exposure treatment to prevent HPS after exposure by the respiratory route.

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).

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.

[Cardiopulmonary syndrome in hantavirus infection (an overview)].

The article provides an overview of domestic and foreign literature on modern aspects of hantavirus infection. Hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome have a high epidemiological significance for Russia's Armed Forces and the armies of many foreign countries. Current knowledge of the various manifestations of the disease contribute to the improvement of diagnosis and timely delivery of medical and preventive measures.

DNA vaccine-generated duck polyclonal antibodies as a postexposure prophylactic to prevent hantavirus pulmonary syndrome (HPS).

Andes virus (ANDV) is the predominant cause of hantavirus pulmonary syndrome (HPS) in South America and the only hantavirus known to be transmitted person-to-person. There are no vaccines, prophylactics, or therapeutics to prevent or treat this highly pathogenic disease (case-fatality 35-40%). Infection of Syrian hamsters with ANDV results in a disease that closely mimics human HPS in incubation time, symptoms of respiratory distress, and disease pathology. Here, we evaluated the feasibility of two postexposure prophylaxis strategies in the ANDV/hamster lethal disease model. First, we evaluated a natural product, human polyclonal antibody, obtained as fresh frozen plasma (FFP) from a HPS survivor. Second, we used DNA vaccine technology to manufacture a polyclonal immunoglobulin-based product that could be purified from the eggs of vaccinated ducks (Anas platyrhynchos). The natural "despeciation" of the duck IgY (i.e., Fc removed) results in an immunoglobulin predicted to be minimally reactogenic in humans. Administration of ≥ 5,000 neutralizing antibody units (NAU)/kg of FFP-protected hamsters from lethal disease when given up to 8 days after intranasal ANDV challenge. IgY/IgYΔFc antibodies purified from the eggs of DNA-vaccinated ducks effectively neutralized ANDV in vitro as measured by plaque reduction neutralization tests (PRNT). Administration of 12,000 NAU/kg of duck egg-derived IgY/IgYΔFc protected hamsters when administered up to 8 days after intranasal challenge and 5 days after intramuscular challenge. These experiments demonstrate that convalescent FFP shows promise as a postexposure HPS prophylactic. Moreover, these data demonstrate the feasibility of using DNA vaccine technology coupled with the duck/egg system to manufacture a product that could supplement or replace FFP. The DNA vaccine-duck/egg system can be scaled as needed and obviates the necessity of using limited blood products obtained from a small number of HPS survivors. This is the first report demonstrating the in vivo efficacy of any antiviral product produced using DNA vaccine-duck/egg system.