Safety and Immunogenicity of Intranasal BPZE1 Vaccination in Healthy Adults

This is a phase 2a, single center, randomized, partially blind, placebo controlled, clinical
trial evaluating a single intranasal dose of either 10^7 colony forming units (CFU) or 10^9
CFU of BPZE1 in healthy adults. The study will evaluate a lyophilized formulation of the
product, with the goal of testing for the optimal dose for subsequent clinical trials. Fifty
healthy adults, 18-49 years of age will be randomized to one of the four following treatment
groups in a 3:3:3:1 ratio: 10^7 CFU of BPZE1 administered by VaxINator device, 10^9 CFU of
BPZE1 administered by VaxINator device, placebo administered by VaxINator device, 10^9 CFU of
BPZE1 administered by needleless tuberculin syringe. Study duration will be approximately 12
months with a subject participation duration of approximately 6 months. The primary objective
of this study is to assess the safety and tolerability of a single intranasal dose of either
10^7 or 10^9 CFU of lyophilized BPZE1 vaccine. The secondary objectives of this study are: 1)
to assess the humoral immunogenicity of lyophilized BPZE1 vaccine at Day 15, Day 29 and Day
181 following receipt of one intranasal dose of 10^7 or 10^9 CFU of BPZE1; 2) to assess
mucosal immunogenicity of lyophilized BPZE1 vaccine at Day 29 and Day 181 following receipt
of one intranasal dose of 10^7 or 10^9 CFU of BPZE1; 3) to evaluate nasal clearance of BPZE1
by culture at Day 29 (and if still positive, at Day 46) following receipt of one intranasal
dose of lyophilized BPZE1 vaccine of 10^7 or 10^9 CFU of BPZE1.

Inclusion Criteria:

Subjects eligible to participate in this study must meet all inclusion criteria:

1. Provide written informed consent prior to initiation of any study procedures.

2. Able to understand and comply with planned study procedures and be available for all
study visits.

3. Males or non-pregnant females, 18-49 years of age, inclusive.

4. 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 because 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, if it is 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 after 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 and inhaled medications (with the exception of inhaled or nasal
corticosteroids within 30 days prior to enrollment), herbals, vitamins, and
supplements are permitted.

5. Oral temperature is < / = 100 degrees Fahrenheit.

6. Pulse is 45 to 100 bpm, inclusive*. *Pulse can be 45 to 50 bpm, inclusive, if no other
symptoms are present. Otherwise, pulse should be 50-100 bpm.

7. Systolic blood pressure is 85 to 150 mm Hg, inclusive.

8. Diastolic blood pressure is 55 to 95 mm Hg, inclusive.

9. White blood cell count is 3,900 cells/microliter or greater.

10. Hemoglobin is 13.0 g/dL or greater (men) or 11.8 g/dL or greater (women).

11. Platelet count is 135,000 cells/microliter or greater.

12. Alanine aminotransferase is < 45 U/L (women) or 62 U/L (men).

13. Serum creatinine is < / = 1.25 mg/dL (men) or 1.11 mg/dL (women).

14. Negative serum HIV antibody assay.

15. Women of childbearing potential* must use an acceptable contraception method** from 30
days before study vaccination until 60 days after vaccination.

- Not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy,
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 has passed
since the last menses if menopausal.

- Includes non-male sexual relationships, abstinence from sexual intercourse
with a male partner, monogamous relationship with vasectomized partner who
has been vasectomized for 180 days or more prior to the subject receiving
study vaccination, barrier methods such as condoms or diaphragms/cervical
caps with spermicide, effective intrauterine devices, NuvaRing(R), and
licensed hormonal methods such as implants, injectables or oral
contraceptives ("the pill").

16. Women of childbearing potential must have a negative urine or serum pregnancy test
within 24 hours prior to study vaccination.

Exclusion Criteria:

1. 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.

2. Have known or suspected active chronic autoinflammatory condition.

3. Have known active neoplastic disease (excluding non-melanoma skin cancer) or a history
of any hematologic malignancy.

4. Have a history of persistent asthma, major anatomic nasopharyngeal abnormality, or
sinus polyp disease due to chronic sinusitis*.

*If a patient has a history of nasopharyngeal surgery such as, but not limited to
rhinoplasty, tonsillectomy or sinus surgery, adequate healing time per the judgement
of the investigator must occur prior to enrollment.

5. Have known hepatitis B or hepatitis C infection.

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

7. Currently untreated or clinically unstable (in the opinion of the investigator)
schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with
subject compliance or safety evaluations.

8. Have been hospitalized for psychiatric illness, history of suicide attempt, or
confinement for danger to self or others within 5 years prior to study vaccination.

9. Have received corticosteroids (including oral, parenteral, inhaled, nasal, or
intra-articular) of any dose within 30 days prior to study vaccination.

10. Individual with PT serum IgG antibodies > / = 20 IU/mL and / or PRN serum IgG
antibodies > / = 125 IU/ml.

11. Unwilling to refrain from smoking tobacco for 28 days post vaccination.

12. Receipt of immunoglobulin or blood derived products within 90 days of enrollment.

13. Receipt of a vaccine against pertussis in the past 2 years.

14. Receipt of a live vaccine within 30 days of study vaccination or an inactivated
vaccine within 14 days of study vaccination.

15. Planned vaccination with a licensed vaccine within 28 days of study vaccination.

16. History of severe allergic reaction (e.g., anaphylaxis) or Bell's palsy, or
Guillain-Barre syndrome, after a previous dose of any diphtheria toxoid-tetanus
toxoid-, or pertussis-containing vaccine, or encephalopathy within 7 days of
administration of a previous pertussis containing vaccine.

17. History of a progressive neurologic disorder.

18. In close contact* with children less than 1 year of age or contact with persons with
known immunocompromising conditions.

*Close contact includes sharing a household, serving as a healthcare worker, or
working professionally in settings with repeated exposures.

19. Receipt of B. pertussis-active antibiotics* within 7 days prior to vaccination.

*B. pertussis active antibiotics include macrolides, fluoroquinolones,
trimethoprim-sulfamethoxazole, tetracyclines.

20. Known hypersensitivity to any component of the study vaccine.

21. Hypersensitivity to azithromycin, which may be used in the event of ongoing BPZE1
colonization.

22. Any condition that, in the opinion of the investigator, might interfere with
objectives of the study or safety to the individual.

23. Acute illness, including temperature > 100 degrees Fahrenheit within one week prior to
vaccination*.

- Enrollment may be postponed if acute illness occurs; subjects must remain within
the screening window, however, and must be rescreened if > 30 days elapses prior
to enrollment.