Safety and Immunogenicity of a Hantaan Virus DNA Vaccine and a Puumala Virus DNA Vaccine, For The Prevention of Hemorrhagic Fever With Renal Syndrome

Inclusion Criteria: Subjects must meet all of the following criteria to be included in the study:

1. Healthy adult male or nonpregnant, nonlactating female, ages 18-49 (inclusive) at thetime of screening
2. Have provided written informed consent before screening
3. Completion of Study Comprehension Quiz (minimum passing score of 80% with 2 attemptspermitted).
4. A subject must have a valid state or government-issued photo ID (eg, driver's license,military ID, or U.S. passport) & be able to pass a background check in order to gainaccess to the base & participate.
5. Free of clinically significant health problems, as determined by pertinent medicalhistory and clinical examination with ECG and laboratory assessments prior to entryinto the study
6. Available and able to participate for all study visits and procedures
7. Females subjects must have had a hysterectomy or bilateral oopherectomy or must beusing an effective method of contraception** from 30 days prior to the first studyvaccination until 90 days after the last study vaccination. ** For this study, we define an effective contraceptive method as one that results ina failure rate of less than 1% per year when it is used consistently and correctly.This includes, but is not limited to, abstinence from sexual intercourse with a malepartner, monogamous relationship with a vasectomized partner, bilateral tuballigation, or intrauterine devices.
8. Female subjects who have not had a hysterectomy or bilateral oopherectomy must have anegative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to each study vaccination.
9. Sexually active male participants whose partner is a woman who has not had ahysterectomy or bilateral oopherectomy and has not had a vasectomy** must agree not tofather a child until 90 days after the last vaccination. ** performed > 1 year prior to screening
10. Women agree to not donate eggs (ova, oocytes) and male subject agrees not to donatesperm from the start of screening onwards until at least 90 days after the lastvaccination.
11. Agree not to participate in another clinical trial during the study period.
12. Agree not to donate blood to a blood bank for 3 months after receiving the last studyvaccine.
13. Have acceptable screening laboratories* within 90 days prior to enrollment. Refer toAppendix A for range of acceptable laboratory values. Screening laboratory values thatare outside acceptable range but are thought to be due to an acute condition or due tolaboratory error may be repeated once. [see Manual of Procedures (MOP)]
14. Negative HIV testing (HIV Ab / antigen 4th generation screen with reflex confirmatoryRNA testing).
15. Negative hepatitis B surface antigen (HBsAg) and hepatitis C antibody testing.

Exclusion Criteria: Subjects meeting any of the following criteria will be excluded from the study:

1. History of previous hantavirus vaccine.
2. History of severe local or systemic reactions to any vaccination or a history ofsevere allergic reactions
3. Ongoing participation in another clinical trial (those continuing through Day 197 willnot join other new studies until their final visit)
4. Receipt of licensed vaccines within 7 days before or after immunization (30 days forlive vaccines)
5. Any use of investigational drugs or vaccines within 30 days before starting the study.
6. Ability to observe possible local reactions at the eligible injection sites (deltoidregion) is, in the opinion of the investigator, unacceptably obscured due to aphysical condition or permanent body art
7. Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, orhepatic or renal functional abnormality as determined by the investigator based onmedical history, physical exam, and/or laboratory screening test
8. Pregnant or lactating female, or female who intends to become pregnant during thestudy period
9. Administration of immunoglobulins and/or any blood products within the 120 dayspreceding study entry or planned administration during the study period
10. Blood donation for human use (eg, American Red Cross or other similar blood drives)within the 56 days preceding study entry or planned administration during the studyperiod
11. Any confirmed evidence of hepatitis B or C infection
12. Have an acute illness*, as determined by the site PI or appropriate sub-investigator,within 72 hours prior to study vaccination. *An acute illness which is nearly resolved with only minor residual symptoms remainingis allowable if, in the opinion of the site PI or appropriate sub-investigator, theresidual symptoms will not interfere with the ability to assess safety parameters asrequired by the protocol. Subjects may re-screen after an acute illness is resolved
13. Any confirmed or suspected immunosuppressive or immunodeficient condition or use ofanticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to studyvaccination.
14. Administration of chronic (defined as more than 14 days) immunosuppressants or otherimmune-modifying drugs within 6 months of study entry

• For corticosteroids, this will mean prednisone, or equivalent, greater than orequal to 0.5 mg/kg/day
• Intranasal, inhaled, and topical steroids are allowed (daily inhaled steroids fortreatment of asthma are NOT allowed)

15. Any chronic or active neurologic disorder, including seizures and epilepsy, excludinga single febrile seizure as a child and intermittent non migraine headaches
16. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or otherpsychiatric diagnosis that may interfere with subject compliance or safetyevaluations.
17. Have any plan to have surgery between enrollment and the end of the study.
18. Have been hospitalized for psychiatric illness, history of suicide attempt, orconfinement for danger to self or others within 10 years prior to study vaccination.
19. Have received any antiviral within 3 days of study vaccination.
20. A diagnosis of Type I or II diabetes.
21. Suspected or known current alcohol or drug abuse. Alcohol abuse defined by an alcoholintake of greater than 3 drinks a day on average for a man, and greater than 2 drinksa day on average for a woman.
22. Unwilling to allow storage and use of blood for future hantavirus-related research
23. Any other significant finding that in the opinion of the investigator would increasethe risk of the individual having an adverse outcome from participating in this study