A Safety and Immunogenicity Study of Intranasal Sendai Virus Vectored Respiratory Syncytial Virus (SeVRSV) Vaccine in Healthy Adults

This is a Phase I randomized, double blind, placebo controlled trial in up to 25 males and
non-pregnant females, 18-45 years old, inclusive, who are in good health and meet all
eligibility criteria. This trial is designed to assess the safety, reactogenicity and
immunogenicity of a single intranasal dose of Sendai virus vectored Respiratory Syncytial
Virus (SeVRSV) vaccine. The subjects will be randomly assigned in a 4:1 ratio to receive
SeVRSV vaccine at a dose of 1 x 10^7 EID50 or placebo (saline) intranasally. Since this is a
first in human, phase I study, the first two subjects (sentinels) will be enrolled in the
SeVRSV treatment arm. Safety and laboratory data will be collected through 14 days post
vaccination. If none of the predefined halting criteria of sentinel subjects are met,
enrollment of the remaining subjects will proceed. If any of the pre-defined halting criteria
of sentinel subjects are met, an electronic review by the SMC will be required prior to
continuation of the study. While safety is evaluated for the sentinel subjects, no new
subjects will be enrolled, but screening may continue. Study duration is approximately 11
months with subject participation duration approximately 6 months. The primary objectives are
to: 1) assess the safety and reactogenicity of SeVRSV vaccine following receipt of one
intranasal dose; 2) assess the ELISA antibody responses to SeV and to the RSV F protein at 28
days post receipt of one intranasal dose of SeVRSV vaccine; 3) assess the detection of
vaccine virus from nasal washes at days 3, 5, 8 and 15 following receipt of one intranasal
dose of SeVRSV vaccine.

Inclusion Criteria:

1. Provide written informed consent before initiation of any study procedures. 2. Are able
to understand and comply with planned study procedures and be available for all study
visits/phone calls.

3. Males or non-pregnant females 18-45, inclusive. 4. Are in good health.

- As determined by medical history and physical examination to evaluate acute or
currently ongoing chronic medical diagnoses or conditions, defined as those that have
been present for at least 90 days that would affect the assessment of the safety of
subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or
conditions should be stable for the last 60 days. This includes no change in chronic
prescription medication, dose, or frequency as a result of deterioration of the
chronic medical diagnosis or condition in the 60 days prior to enrollment. Any
prescription change that is due to change of health care provider, insurance company,
etc., or that is done for financial reasons, as long as in the same class of
medication, will not be considered a deviation of this inclusion criterion. Any change
in prescription medication due to improvement of a disease outcome, as determined by
the site principal investigator or appropriate sub-investigator, will not be
considered a deviation of this inclusion criterion. Subjects may be on chronic or as
needed (prn) medications if, in the opinion of the site principal investigator or
appropriate sub-investigator, they pose no additional risk to subject safety or
assessment of reactogenicity and immunogenicity and do not indicate a worsening of
medical diagnosis or condition. Similarly, medication changes subsequent to enrollment
and study vaccination are acceptable provided there was no deterioration in the
subject's chronic medical condition that necessitated a medication change, and there
is no additional risk to the subject or interference with the evaluation of responses
to study vaccination. Note: Topical, nasal, and inhaled medications (with the
exception of steroids as outlined in the Subject Exclusion Criteria), herbals,
vitamins, and supplements are permitted.

5. Oral temperature is less than 100.0 degrees Fahrenheit. 6. Pulse is 47 to 105 beats
per minute (bpm), inclusive. 7. Systolic blood pressure (BP) is 85 to 150 mm Hg,
inclusive. 8. Diastolic blood pressure (BP) is 55 to 95 mmHg, inclusive. 9. Women of
childbearing potential must use an acceptable method of contraception from 30 days
prior to study vaccination until 60 days after study vaccination.

- Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy, or
successful Essure (R) placement (permanent, non-surgical, non-hormonal
sterilization) with documented radiological confirmation test at least 90 days
after the procedure, and still menstruating or < 1 year of the last menses if
menopausal.

--- Includes, but is not limited to, non-male sexual relationships, abstinence
from sexual intercourse with a male partner, monogamous relationship with a
vasectomized partner, male condoms with the use of applied spermicide,
intrauterine devices, NuvaRing (R), and licensed hormonal methods such as
implants, injectables or oral contraceptives ("the pill").

10. Female subjects of childbearing potential must have a negative serum
pregnancy test at screening and a negative urine pregnancy test within 24 hours
prior to study vaccination.

11. Sexually active males with a woman of childbearing potential and has not had
a vasectomy performed > 1 year prior to screening must agree not to father a
child for 60 days after vaccination.

- See criteria of women of childbearing potential above. ----- Must agree to
use a barrier method of birth control e.g., either condom with spermicidal
foam/gel/film/cream/suppository or partner uses occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

11. Erythrocyte sedimentation rate (ESR) is less than 30 mm per hour. 12.
White blood cells (WBC) are greater than 4.4 x 10^3/uL and less than 11.1 x
10^3/uL.

13. Hemoglobin (Hgb) is greater than 11.6 g/dL for females or is greater
than 13.2 g/dL for males.

14. Platelets are greater than 134 x 10^3/uL and less than 466 x 10^3/uL.
15. Absolute Neutrophil Count is greater than 1.7 x 10^3/uL

------ For subjects who are of African American or Middle Eastern decent,
ANC must be greater than 0.8 x 10^3/uL for inclusion.

16. Alanine aminotransferase (ALT) is less than 1.25 ULN for females and
males. 17. Aspartate aminotransferase (AST) is less than 1.25 ULN for
females and males.

18. Total bilirubin is less than 1.11 mg/dL. 19. Creatinine is less than
0.96 mg/dL for females or is less than 1.18 mg/dL for males.

20. Sodium is greater than 135 mmol/L and less than 146 mmol/L. 21.
Potassium is greater than 3.4 mmol/L and less than 5.2 mmol/L. 22. BUN is
less than 19 mg/dL (BUN will be obtained only if creatinine is above normal
range).

23. HgbA1C is less than 6.3%. 24. Have normal screening laboratories for
urine protein. Trace protein is acceptable.

25. Drug screen for opiates is negative. 26. Have a normal ECG.

- Abnormal screening electrocardiogram (ECG) defined as pathologic Q
waves and significant ST-T wave changes: criteria for left ventricular
hypertrophy; and any non-sinus rhythm excluding isolated premature
atrial contractions.

27. Agrees not to participate in another clinical trial during the
study period.

28. Agrees not to donate blood or blood products to a blood bank for 6
months after receiving the vaccine.

Exclusion Criteria:

1. 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
remaining is allowable if, in the opinion of the site PI or appropriate
sub-investigator, the residual symptoms will not interfere with the ability to assess
safety parameters as required by the protocol. Subjects may re-screen after an acute
illness is resolved.

2. Have any medical disease or condition that, in the opinion of the site PI or
appropriate sub-investigator, is a contraindication to study participation.

-- Including acute or chronic medical disease or condition, defined as persisting for
at least 90 days, that would place the subject at an unacceptable risk of injury,
render the subject unable to meet the requirements of the protocol, or may interfere
with the evaluation of responses or the subject's successful completion of this study.

3. History of anatomic disorder of the nares or nasopharynx (Deviated septum is allowed).

4. History of chronic sinus infections.

5. A diagnosis of type I or II diabetes.

6. Have a body mass index (BMI) < 18.5 or > / = 35 kg/m^2.

7. History of medical diagnosis of selected respiratory diseases.

--- Asthma as an adult (defined as diagnosis at > / = 18 years of age), reactive
airway disease, wheezing requiring medication as an adult (defined as diagnosis at > /
= 18 years of age), cystic fibrosis, bronchopulmonary dysplasia, chronic pulmonary
disease, medically confirmed apnea, hospitalization for respiratory illness or
mechanical ventilation for respiratory illness.

8. History of smoking in the last 5 years.

9. Have immunosuppression as a result of an underlying illness or treatment, or use of
anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study
vaccination.

10. Have known active neoplastic disease or a history of any hematologic malignancy.
Non-melanoma skin cancers that are not active are permitted.

11. Positive hepatitis C, or HIV serology or positive hepatitis B serology not consistent
with prior hepatitis B immunization.

12. History of Bell's Palsy.

13. History of anosmia (per subject report of ever having symptoms or clinician
diagnosis).

14. Have known hypersensitivity or allergy to eggs, or other components of the study
vaccine.

15. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.

16. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other
psychiatric diagnosis that may interfere with subject compliance or safety
evaluations.

17. Have been hospitalized for psychiatric illness, history of suicide attempt, or
confinement for danger to self or others within 10 years prior to study vaccination.

18. Have taken oral or parenteral (including intraarticular) corticosteroids of any dose
within 30 days prior to study vaccination.

19. Have taken high-dose inhaled corticosteroids within 30 days prior to study
vaccination.

---- High-dose defined using the inhaled high-dose reference chart.

20. Receipt of any intranasal medication within 7 days prior to study vaccination through
14 days post study vaccination.

21. Received any licensed live vaccine within 30 days of study vaccination.

22. Received a licensed inactivated vaccine within 14 days of the study vaccination.

23. Received immunoglobulin or other blood products (with exception of Rho D
immunoglobulin) within 90 days prior to study vaccination.

24. Received an experimental agent within 28 days prior to study vaccination, or expects
to receive an experimental agent during the 6-month trial-reporting period.

----- Including vaccine, drug, biologic, device, blood product, or medication.

------ Other than from participation in this study.

25. Female subjects who are breastfeeding or plan to breastfeed at any given time from the
receipt of study vaccination throughout the 6 month trial period.

26. Expected household contact or same room contact for > 1 hour with children < 6 months
of age or immunocompromised individuals within 7 days of receipt of study vaccination.

27. Day care provider or healthcare provider with direct contact with children or
patients.

28. Have received any antiviral drug within 3 days of study vaccination.

29. Any condition that would, in the opinion of the Site Investigator, place the subject
at an unacceptable risk of injury or render the subject unable to meet the
requirements of the protocol.