Phase 1 Norwalk Vaccine Study
Phase 1 Norwalk Vaccine Study
Randomized, double blind, multi-site, study in healthy adults, comparing safety and
 immunogenicity of two dosage levels of Norwalk VLP Vaccine with adjuvant/excipients and with
 placebo controls

 Primary Objective:

 -  Safety as determined by occurrence of local intranasal symptoms or other symptoms as
 reported by a self-administered memory aid for 7 days after each vaccination and
 hematology, blood chemistry and physical examinations performed by the clinical research
 staff

 -  Subjects will also be monitored for Serious Adverse Events (SAEs), and onset of any new
 medical conditions for 180 days following the last study vaccinations (Day 201).

 Secondary Objectives

 Evaluations of immunogenicity as determined by:

 -  Geometric mean titers and seroconversion rate of serum anti- Norwalk VLP IgG and IgA

 -  Stimulation of anti-Norwalk VLP IgA antibody secreting cells (ASC)

 -  Presence of antigen specific memory B-cell response

 Cells will be collected and stored for possible future evaluation of Norwalk VLP-specific
 cell-mediated immune (CMI) responses

 Study Hypothesis:

 The incidence of adverse events after intranasal Norwalk VLP Vaccine will be the same as the
 incidence of adverse events after intranasal adjuvant/excipients alone. Norwalk VLP Vaccine
 and adjuvant/excipients will have a higher incidence of mild to moderate nasal adverse events
 compared to placebo but similar incidence of other adverse events.

 Two doses of the 100 µg of Norwalk VLP Vaccine will be more immunogenic than two doses of 50
 µg of Norwalk VLP Vaccine. The post-vaccination serum antibody responses, the number of
 antibody secreting cells (ASC) and IgG and IgA memory B-cell responses directed against
 Norwalk Virus antigen will be increased after Norwalk VLP Vaccine compared to
 adjuvant/excipients and to placebo.
Inclusion Criteria:

 1. Signed written informed consent

 2. Age 18 - 50 years, inclusive

 3. Good general health as determined by a screening evaluation within 30 days before
 administration of Norwalk VLP Vaccine, adjuvant/excipients or placebo

 4. Expressed interest and availability to fulfill the study requirements

 5. Agrees not to become pregnant from the time of study enrollment until at least 56 days
 after the last administration of Norwalk VLP Vaccine, adjuvant/excipients or placebo;
 if a woman is sexually active and capable of conception (i.e., no history of
 hysterectomy or tubal ligation), she must agree to use hormonal or barrier birth
 control. A woman is eligible if she is monogamous with a male who has had a vasectomy.

 6. Demonstrated to be an H type-1 antigen secretor

 7. Agrees not to participate in another clinical trial with an investigational product
 for the entire duration of the study (six months after the last study dose i.e. 201
 days)

 8. Agrees to storage of unused clinical specimens for an indefinite period of time only
 for those specimens collected by the University of Maryland CVD for use in future
 research at the CVD. [A University of Maryland site-specific inclusion criterion]

 Exclusion Criteria

 1. History of any of the following medical illnesses

 -  Chronic rhinitis, runny nose, sneezing

 -  Clinically significant nose bleed within the last year

 -  Diabetes

 -  Cancer

 -  Heart disease (hospitalization for a heart attack, arrhythmia, or syncope)

 -  Unconsciousness (other than a single brief "concussion")

 -  Seizures (other than febrile seizures as a child <5 years old)

 -  Recurrent infections (more than 3 hospitalizations for invasive bacterial
 infections such as pneumonia or meningitis)

 -  Asthma requiring treatment with inhaler or medication

 -  Any current illness requiring daily medication other than vitamins, birth
 control, or anti-depressant

 2. Blood Type B or AB, regardless of Rh + or -

 3. Allergies or hypersensitivity to chitosan, shrimp, other shellfish or any component of
 the vaccine, adjuvant/excipients or placebo

 4. History of nasal surgery of any type (including tonsilectomy/adenoidectomy)

 5. Any clinically significant abnormality detected on physical examination, including:

 -  Murmur (other than a functional murmur)

 -  Focal neurological abnormality

 -  Hepatosplenomegaly

 -  Lymphadenopathy

 -  Jaundice

 6. Hypertension (BP > 140/90 mm Hg on two separate days)

 7. Any lab abnormality, as listed below:

 -  Neutrophils (WBC) outside the normal range

 -  Hemoglobin outside the normal range (may be repeated once if outside this limit)

 -  Platelet count outside the normal range (may be repeated once if outside this
 limit)

 -  Creatinine outside the normal range (may be repeated once if outside this limit)

 -  Glucose > upper limit of normal (may be repeated once if outside this limit)

 -  AST or ALT outside the normal range (may be repeated once if outside this limit)

 -  Positive serology for hepatitis C or HIV antibody or hepatitis B surface antigen

 8. For women, positive serum pregnancy test within 7 days and urine pregnancy test within
 24 hours of administering either dose of Norwalk VLP Vaccine, adjuvant/excipients or
 placebo

 9. Nursing mother

 10. Temperature > 38.0 degrees C (100.4 degrees F) or symptoms of an acute self-limited
 illness such as an upper respiratory infection or gastroenteritis within 3 days of
 administration of Norwalk VLP Vaccine, adjuvant/excipients or placebo

 11. Previous participation in a study of Norovirus vaccines

 12. Medical, occupational, or family problems as a result of alcohol or illicit drug use
 during the past 12 months

 13. Receipt of an investigational vaccine or drug within 28 days before administration of
 Norwalk VLP Vaccine, adjuvant/excipients or placebo

 14. Other condition that in the clinical judgment of the investigator would jeopardize the
 safety or rights of a subject participating in the trial, would render the subject
 unable to comply with the protocol or would interfere with the evaluation of the
 vaccine

 15. Failure to pass written examination about this study (70% correct answers required to
 pass)[A University of Maryland site-specific exclusion criterion]