This study is an open-label, dose-escalating Phase 1 investigation of S. flexneri 2a
InvaplexAR vaccine. A total of up to 40 subjects will receive one of four S. flexneri 2a
InvaplexAR vaccine doses. The vaccine will be administered intranasally (without adjuvant).
The vaccine will be administered on Days 0,14, and 28. Volunteers (10 per group [8 minimum])
will receive the same dose at each vaccination dependent upon group assignment. Groups will
be divided according to the table below. An interval no less than 1 week will separate the
third dose of a group from the first dose of the next group (receiving an increased
InvaplexAR dose). Blood, stool, and saliva specimens will be collected at pre-specified
intervals to examine systemic and mucosal vaccine antigen-specific immune responses. Ocular
tear samples will be collected in groups C and D. Vaccine safety will be actively monitored
during vaccination and for 28 days following the third vaccine dose. The decision to advance
to the next dose level is based on the safety assessment (not immunogenicity). A dose level
with no occurrence of stopping criteria in the 7 days following the last vaccine dose will
prompt moving to the next higher level. All safety data will be summarized and reviewed with
the research monitor prior to dose escalation. In addition, a report of all safety data will
be provided to the sponsor's safety office for informational purposes.
- Healthy, adult, male or female, age 18 to 45 years (inclusive) at the time of
- Completion and review of comprehension test (achieved > 70% accuracy).
- Signed informed consent document.
- Available for the required follow-up period and scheduled clinic visits.
- Women: Negative pregnancy test with understanding (through informed consent process)
to not become pregnant nor to breastfeed during the study or within 3 months following
- Health problems (for example, chronic medical conditions such as psychiatric
conditions, diabetes mellitus, hypertension, or any other conditions that might place
the subjects at increased risk of adverse events)- study clinicians, in consultation
with the PI, will use clinical judgment on a case-by-case basis to assess safety risks
under this criterion. The PI will consult with the Research Monitor as appropriate.
- Clinically significant abnormalities on physical examination (chronic sinusitis or
seasonal rhinitis) which compromise identification and interpretation of potential
vaccine associated adverse effects.
- Use of immunosuppressive and/or immunomodulative drugs such as corticosteroids or
chemotherapeutics that may influence antibody development.
- Immunosuppressive illnesses (including IgA deficiency defined by serum IgA below level
of detection or <7mg/dL).
- Participation in research involving another investigational product (defined as
receipt of an investigational product or exposure to an invasive investigational
device) 30 days before planned date of first vaccination or anytime throughout the
duration of the study until the last study safety visit.
- Positive blood test for HBsAG, HCV, HIV-1/HIV-2.
- Clinically significant abnormalities on basic laboratory screening.
- Presence of significant unexplained laboratory abnormalities that in the opinion of
the PI may potentially confound the analysis of the study results.
- Current smoker or smoker in past 1 year ('smoker' defined as daily cigarette, cigar,
or pipe use for a period of at least 1 month).
- Structural abnormalities on sinus/nasal cavity examination.
- Nasal polyps.
- Nasal ulcers.
- Deviated nasal septum. This question is being used to determine whether the volunteer
has a clinically significant deviated septum that causes nasal obstruction (thereby
causing difficulty breathing), interferes with normal sinus drainage, or obscures
visualization of the posterior nasal cavity complicating examination and safety
- Chronic sinusitis/rhinitis.
- Current or planned use of nasal topical corticosteroids and/or nasal spray medications
in the 4 weeks prior to dosing or during the study vaccination period.
- Current or recent history (in the past 5 years) of reactive airway disease (asthma),
chronic obstructive pulmonary disease, or chronic bronchitis.
- History of Bell's palsy.
- Chronic use (weekly or more often) of anti-diarrheal, anti-constipation, or antacid
therapy (excluding use associated with spicy meals).
- Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on
a regular basis; loose or liquid stools on other than an occasional basis.
- Personal or family history of inflammatory arthritis.
- Positive blood test for HLA-B27.
- History of allergy to any vaccine.
Prior Exposure to Shigella
- Serum IgG titer ≥ 2500 to Shigella flexneri 2a LPS.
- History of microbiologically confirmed Shigella infection in the past 3 years.
- Received previous experimental Shigella vaccine or live Shigella challenge.
- Travel to countries with symptoms of travelers' diarrhea where Shigella or other
enteric infections are endemic (most of the developing world) within the past 6 months
prior to dosing.
- Occupation involving handling of Shigella bacteria currently, or in the past 3 years.
Christopher Duplessis, MD, MPH, MS
Enteric Diseases Department Naval Medical Research Center