Safety and Immunogenicity of Artificial Invaplex (Shigella Flexneri 2a InvaplexAR)
Condition: Shigellosis; Bacillary Dysentery
MeSH terms: Dysentery, Bacillary; Dysentery
Intervention: Shigella flexneri 2a InvaplexAR
Intervention description: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      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).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy, adult, male or female, age 18 to 45 years (inclusive) at the time of
             enrollment.

          -  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
             last vaccination

        Exclusion Criteria:

          -  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).

        Research specific

          -  Structural abnormalities on sinus/nasal cavity examination.

          -  Rhinoplasty.

          -  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
             monitoring..

          -  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.