Phase I Study of a Vaccine for Severe Acute Respiratory Syndrome (SARS)
Phase I Study of a Vaccine for Severe Acute Respiratory Syndrome (SARS)
This study will test whether an experimental vaccine to protect against severe acute
 respiratory syndrome (SARS) is safe, causes any side effects, and causes an immune response.
 SARS affects the respiratory system, usually starting with fever and muscle aches. Patients
 may get a dry cough and have difficulty breathing. Infection may be mild, but it can lead to
 death.

 Vaccines contain substances from an infectious agent, such as a virus, that, when injected
 into a person's body, stimulates production of antibodies that create resistance, or
 immunity, to that agent. The vaccine in this study contains genetic material (DNA) that codes
 for a protein found in the virus that causes SARS. Injected into a muscle, it instructs the
 body to make a small amount of a SARS protein. The vaccine is made from just one small part
 of the code for one SARS protein; a person cannot get SARS from the vaccine.

 Normal volunteers between 18 and 50 years of age who are in general good health may be
 eligible for this 32-week study. Candidates are screened with a physical examination and
 blood and urine tests.

 Participants have nine clinic visits during the study. They receive three vaccine injections,
 given with a system called the Bioinjector 2000® (Registered Trademark), which delivers the
 vaccine through the skin without the use of a needle. Following each injection, participants
 take home a diary card, on which they record their temperature and any vaccine side effects
 daily for 5 days. Participants must immediately report any symptoms to a study physician,
 and, if necessary, go to the clinic for an examination. Participants have the following tests
 and procedures:

 -  Vaccine injections (study day 0, around week 4, and around week 8, with at least 21 days
 between injections)

 -  Medical history and, if needed, physical examination (study day 0 and weeks 2, 4, 6, 8,
 10, 12, 24, and 32)

 -  Check of vital signs and weight (study day 0 and weeks 2, 4, 6, 8, 10, 12, 24 and 32)

 -  Lymph node examination (day 0 and weeks 2, 4, 6, 8, 10 and 12)

 -  Blood draw (study day 0 and weeks 2, 4, 6, 8, 10, 12, 24 and 32)

 -  Pregnancy test for women (day 0 and weeks 4, 8 and 32)

 -  Urine sample (day 0 and weeks 2, 4, 6, 8, 10)
Study Design: This is a Phase I open label study to evaluate safety, tolerability, and immune
 response of a recombinant DNA vaccine, VRC-SRSDNA015-00-VP. The hypothesis is that this
 regimen will be safe for human administration and elicit immune responses to the SARS
 coronavirus (CoV) spike (S) protein. The primary objective is to evaluate the safety and
 tolerability in humans of the investigational vaccine. Secondary and exploratory objectives
 are related to the immunogenicity of the study vaccine.

 Product Description: VRC-SRSDNA015-00-VP is composed of a single closed, circular DNA plasmid
 that is based on the S protein of SARS-CoV. Vaccine vials will be supplied at 4 mg/mL. Each
 DNA vaccination will be 1 mL of vaccine administered intramuscularly (in deltoid muscle)
 using the Biojector 2000 Needle-Free Injection Management System.

 Subjects: Healthy adult volunteers (18 to 50 years old) will be enrolled.

 Study Plan: Ten volunteers will be enrolled and receive 3 injections on the schedule shown in
 the schema. The protocol requires nine clinic visits and three telephone follow-up contacts.

 Study Duration: 32 weeks clinical follow-up for each participant.

 Study Endpoints: The primary endpoint is safety of the regimen; secondary immunogenicity
 endpoints are an intracellular cytokine staining (ICS) assay for SARS specific T cell
 responses and an assay for antibody-dependent enhancement of virus uptake. The principal
 timepoints for ICS are Week 0 (baseline) and Weeks 6, 8, 10 and 12. ICS at other study
 timepoints, as well as other immunogenicity assays through Week 32, will be completed as
 exploratory evaluations.
-  INCLUSION CRITERIA:

 A participant must meet all of the following criteria:

 18 to 50 years old.

 Available for clinical follow-up through Week 32 of the study.

 Able to provide proof of identity to the satisfaction of the study clinician completing the
 enrollment process.

 Complete an Assessment of Understanding prior to enrollment and verbalize understanding of
 all questions answered incorrectly.

 Able and willing to complete the informed consent process.

 Willing to receive HIV test results and wiling to abide by NIH guidelines for partner
 notification of positive HIV results.

 Willing to donate blood for sample storage to be used for future research.

 In good general health without clinically significant medical history and has
 satisfactorily completed screening.

 Physical examination and laboratory results without clinically significant findings within
 the 28 days prior to enrollment.

 Laboratory Criteria within 28 Days prior to Enrollment:

 Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to 13.5 g/dL
 for men.

 WBC = 3,300-12,000 cells/mm(3).

 Absolute neutrophil count (ANC) within institutional normal range.

 Total lymphocyte count greater than or equal to 800 cells/mm(3).

 Platelets within institutional normal limits.

 ALT (SGPT) less than or equal to upper limit of normal.

 Serum creatinine less than or equal to upper limit of normal.

 Normal urinalysis defined as negative glucose, negative or trace protein, and no clinically
 significant blood in the urine.

 Negative FDA-approved HIV blood test. (Note: Results of HIV ELISA will be documented, but a
 negative HIV PCR will be sufficient for eligibility screening of subjects with positive HIV
 ELISA that is due to prior participation in an HIV vaccine study).

 Negative Hepatitis B surface antigen.

 Negative anti-HCV (hepatitis C virus antibody) and negative HCV PCR.

 Female Specific Criteria:

 Negative beta-HCG pregnancy test (urine or serum) on day of enrollment for women presumed
 to be of reproductive potential.

 A female participant must meet any of the following criteria:

 No reproductive potential because of menopause [one year without menses] or because of a
 hysterectomy, bilateral oophorectomy, or tubal ligation;

 Or

 Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and
 through Week 32 of the study;

 Or

 Participant agrees to consistently practice contraception at least 21 days prior to
 enrollment and through Week 32 of the study by one of the following methods:

 Condoms, male or female, with or without a spermicide;

 Diaphragm or cervical cap with spermicide;

 Intrauterine device;

 Contraceptive pills or patch, Norplant, Depo-Provera or other FDA-approved contraceptive
 method;

 Male partner has previously undergone a vasectomy for which there is documentation.

 EXCLUSION CRITERIA:

 A volunteer will be excluded if one or more of the following conditions apply:

 Women:

 Woman who is breast-feeding or planning to become pregnant during the 32 weeks of study
 participation.

 Volunteer has received any of the following substances:

 Immunosuppressive medications or cytotoxic medications or inhaled corticosteroids within
 the past six months (with the exception of corticosteroid nasal spray for allergic rhinitis
 or topical corticosteroids for an acute uncomplicated dermatitis).

 Blood products within 120 days prior to HIV screening.

 Immunoglobulin within 60 days prior to HIV screening.

 Investigational research agents within 30 days prior to initial study vaccine
 administration.

 Live attenuated vaccines within 30 days prior to initial study vaccine administration.

 Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or allergy
 treatment with antigen injections, within 14 days of study vaccine administration.

 Current anti-TB prophylaxis or therapy.

 Volunteer has a history of any of the following clinically significant conditions:

 Serious adverse reactions to vaccines such as anaphylaxis, hives, respiratory difficulty,
 angioedema, or abdominal pain.

 Autoimmune disease or immunodeficiency.

 Asthma that is unstable or required emergent care, urgent care, hospitalization or
 intubation during the past two years or that requires the use of oral or intravenous
 corticosteroids.

 Diabetes mellitus (type I or II), with the exception of gestational diabetes.

 History of thyroidectomy or thyroid disease that required medication within the past 12
 months.

 Serious angioedema episodes within the previous 3 years or requiring medication in the
 previous two years.

 Hypertension that is not well controlled by medication or is more than 145/95 at
 enrollment.

 Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet
 disorder requiring special precautions) or significant bruising or bleeding difficulties
 with IM injections or blood draws.

 Malignancy that is active or treated malignancy for which there is not reasonable assurance
 of sustained cure or malignancy that is likely to recur during the period of study.

 Seizure disorder other than: 1) febrile seizures under the age of two, 2) seizures
 secondary to alcohol withdrawal more than 3 years ago, or 3) a singular seizure not
 requiring treatment within the last 3 years.

 Asplenia, functional asplenia or any condition resulting in the absence or removal o the
 spleen.

 Psychiatric condition that precludes compliance with the protocol; past or present
 psychoses; past or present bipolar disorder requiring therapy that has not been well
 controlled on medication for the past two years; disorder requiring lithium; or suicidal
 ideation occurring within five years prior to enrollment.

 Any medical, psychiatric, social condition, occupational reason or other responsibility
 that, in the judgment of the investigator, is a contraindication to protocol participation
 or impairs a volunteer's ability to give informed consent.

 Allergic reaction to aminoglycoside antibiotics.