Safety and Immunogenicity of Artificial Invaplex (Shigella Flexneri 2a InvaplexAR)

• Sponsor: U.S. Army Medical Research and Development Command (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02445963
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arms: 4
• Actual Duration (Months): 7.4
• Patients Per Site Per Month: 5.1

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Shigellosis; Bacillary Dysentery	Biological: Shigella flexneri 2a InvaplexAR	Phase 1

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase 1 Open-label, Dose Escalating Study of Artificial Shigella Flexneri 2a InvaplexAR Administered Intranasally to Healthy, Adult Volunteers to Evaluate Safety and Immunogenicity
• Actual Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: May 13, 2016
• Actual Study Completion Date: May 13, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 10 μg S. flexneri 2a Invaplex 10 subjects vaccinated on days 0, 14, 28	Biological: Shigella flexneri 2a InvaplexAR; 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.
Active Comparator: 50 μg S. flexneri 2a Invaplex 10 subjects vaccinated on days 0, 14, 28	Biological: Shigella flexneri 2a InvaplexAR; 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.
Active Comparator: 250 μg S. flexneri 2a Invaplex 10 subjects vaccinated on days 0, 14, 28	Biological: Shigella flexneri 2a InvaplexAR; 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.
Active Comparator: 500 μg S. flexneri 2a Invaplex 10 subjects vaccinated on days 0, 14, 28	Biological: Shigella flexneri 2a InvaplexAR; 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.

Outcome Measures

Primary Outcome Measures

1. Number of Treatment Related Adverse Events [166 days]

   Number of adverse events related to the vaccine for each arm

2. Antibody Titers Against IgG and IgA Immunizing Antigens [At screening and Days 0, 14, 28, 35, 42, and 56]

   Serum samples will be assayed for antibody titers against the immunizing antigens LPS, IpaB, IpaC, and S. flexneri 2a Invaplex at screening, and Days 0, 14, 28, 35, 42, and 56 for 36 subjects. Previously established high-titer specimens will be included on each plate to track day to day interassay variation. For each antigen, pre- and post-vaccination serum samples will be assayed side-by-side. The antibody titer assigned to each sample will represent the geometric mean of duplicate tests performed on 2 different days. Reciprocal endpoint titers < 5 will be assigned a value of 2.5 for computational purposes. Seroconversion will be defined as a > 4-fold increase in endpoint titer between pre-and post-vaccination samples AND a post-vaccination reciprocal titer >10.

Secondary Outcome Measures

1. IgG and IgA Antigen-Specific Antibody Secreting Cell (ASC) Mucosal Responses [56 Days]

   ASC responses were assessed using isolated peripheral blood mononuclear cells (PBMCs). For each antigen, pre- and post-vaccination samples were tested on the same plates for total and vaccine-specific numbers. The ASC responses indirectly reflect intestinal immune responses through measurement of antigen-specific B-lymphocytes in systemic circulation before homing to gut effector sites. An ASC response was defined as > 10 ASCs above baseline.

2. IgG and IgA Antigen-Specific Antibody Lymphocyte Supernatant (ALS) Mucosal Responses [56 Days]

   ALS responses were assessed using isolated peripheral blood mononuclear cells (PBMCs). For each antigen, pre- and post-vaccination samples were tested on the same plates for total and vaccine-specific numbers. The ALS responses indirectly reflect intestinal immune responses through measurement of antigen-specific B-lymphocytes in systemic circulation before homing to gut effector sites. An ALS response was defined as a ≥ 4-fold increase over baseline ALS titers.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Walter Reed Army Institute of Research, Clinical Trials Center	Silver Spring	Maryland	United States	20910

Sponsors and Collaborators

• U.S. Army Medical Research and Development Command

Investigators

• Principal Investigator: Christopher Duplessis, MD, MPH, MS, Enteric Diseases Department Naval Medical Research Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: U.S. Army Medical Research and Development Command
• ClinicalTrials.gov Identifier: NCT02445963
• Other Study ID Numbers: S-15-19; A-18716; NMRC.2015.0003
• First Posted: May 15, 2015
• Last Update Posted: Feb 12, 2021
• Last Verified: Feb 1, 2021

• Additional relevant MeSH terms: Dysentery, Bacillary; Dysentery

Study Results

Participant Flow

Arm/Group Title	10 μg S. Flexneri 2a Invaplex	50 μg S. Flexneri 2a Invaplex	250 μg S. Flexneri 2a Invaplex	500 μg S. Flexneri 2a Invaplex
Arm/Group Description	9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.
Period Title: Overall Study
STARTED	9	9	10	10
COMPLETED	7	9	9	10
NOT COMPLETED	2	0	1	0

Baseline Characteristics

Arm/Group Title	10 μg S. Flexneri 2a Invaplex	50 μg S. Flexneri 2a Invaplex	250 μg S. Flexneri 2a Invaplex	500 μg S. Flexneri 2a Invaplex	Total
Arm/Group Description	9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	Total of all reporting groups
Overall Participants	9	9	10	10	38
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	24	34	28	28	28
Sex: Female, Male (Count of Participants)
Female	2 22.2%	5 55.6%	1 10%	2 20%	10 26.3%
Male	7 77.8%	4 44.4%	9 90%	8 80%	28 73.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 11.1%	1 10%	0 0%	2 5.3%
Not Hispanic or Latino	9 100%	8 88.9%	9 90%	10 100%	36 94.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 22.2%	3 33.3%	0 0%	4 40%	9 23.7%
White	7 77.8%	6 66.7%	9 90%	6 60%	28 73.7%
More than one race	0 0%	0 0%	1 10%	0 0%	1 2.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	9 100%	9 100%	10 100%	10 100%	38 100%

Outcome Measures

1. Primary Outcome

Title	Number of Treatment Related Adverse Events
Description	Number of adverse events related to the vaccine for each arm
Time Frame	166 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 μg S. Flexneri 2a Invaplex	50 μg S. Flexneri 2a Invaplex	250 μg S. Flexneri 2a Invaplex	500 μg S. Flexneri 2a Invaplex
Arm/Group Description	9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.
Measure Participants	9	9	10	10
Number [Adverse Events]	27	37	41	46

2. Primary Outcome

Title	Antibody Titers Against IgG and IgA Immunizing Antigens
Description	Serum samples will be assayed for antibody titers against the immunizing antigens LPS, IpaB, IpaC, and S. flexneri 2a Invaplex at screening, and Days 0, 14, 28, 35, 42, and 56 for 36 subjects. Previously established high-titer specimens will be included on each plate to track day to day interassay variation. For each antigen, pre- and post-vaccination serum samples will be assayed side-by-side. The antibody titer assigned to each sample will represent the geometric mean of duplicate tests performed on 2 different days. Reciprocal endpoint titers < 5 will be assigned a value of 2.5 for computational purposes. Seroconversion will be defined as a > 4-fold increase in endpoint titer between pre-and post-vaccination samples AND a post-vaccination reciprocal titer >10.
Time Frame	At screening and Days 0, 14, 28, 35, 42, and 56

Outcome Measure Data

Analysis Population Description

Subjects who received at least 2 vaccine doses were included in the immunology analyses.

Arm/Group Title	10 μg S. Flexneri 2a Invaplex	50 μg S. Flexneri 2a Invaplex	250 μg S. Flexneri 2a Invaplex	500 μg S. Flexneri 2a Invaplex
Arm/Group Description	8 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.
Measure Participants	8	9	9	10
Serum IgG (Invaplex)	1345.4	4703.2	5486.4	5571.5
Serum IgA (Invaplex)	259.4	800.0	685.8	606.3
Serum IgG (LPS)	1902.7	4703.2	4703.2	6400
Serum IgA (LPS)	259.4	635.0	544.3	527.8
Serum IgG (IpaB)	183.4	740.7	342.9	229.7
Serum IgA (IpaB)	50.0	73.5	85.7	50.0
Serum IgG (IpaC)	336.4	2539.8	1728.1	2599.2
Serum IgA (IpaC)	70.7	317.5	272.2	400.0

3. Secondary Outcome

Title	IgG and IgA Antigen-Specific Antibody Secreting Cell (ASC) Mucosal Responses
Description	ASC responses were assessed using isolated peripheral blood mononuclear cells (PBMCs). For each antigen, pre- and post-vaccination samples were tested on the same plates for total and vaccine-specific numbers. The ASC responses indirectly reflect intestinal immune responses through measurement of antigen-specific B-lymphocytes in systemic circulation before homing to gut effector sites. An ASC response was defined as > 10 ASCs above baseline.
Time Frame	56 Days

Outcome Measure Data

Analysis Population Description

Arm 1: One patient was lost to follow-up post dose 1 vaccination, overall participants is therefore 8 for this arm Arm 3: One patient withdrew from the study due to symptoms post dose 1 vaccination, overall participants is therefore 9 for this arm

Arm/Group Title	10 μg S. Flexneri 2a Invaplex	50 μg S. Flexneri 2a Invaplex	250 μg S. Flexneri 2a Invaplex	500 μg S. Flexneri 2a Invaplex
Arm/Group Description	8 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.
Measure Participants	8	9	9	10
ASC IgG (Invaplex)	0.5	4.0	5.0	9.0
ASC IgA (Invaplex)	1.00	27.0	23.0	41.5
ASC IgG (LPS)	0.0	0.0	1.0	2.0
ASC IgA (LPS)	0.0	4.0	1.0	3.0

4. Secondary Outcome

Title	IgG and IgA Antigen-Specific Antibody Lymphocyte Supernatant (ALS) Mucosal Responses
Description	ALS responses were assessed using isolated peripheral blood mononuclear cells (PBMCs). For each antigen, pre- and post-vaccination samples were tested on the same plates for total and vaccine-specific numbers. The ALS responses indirectly reflect intestinal immune responses through measurement of antigen-specific B-lymphocytes in systemic circulation before homing to gut effector sites. An ALS response was defined as a ≥ 4-fold increase over baseline ALS titers.
Time Frame	56 Days

Outcome Measure Data

Analysis Population Description

Arm 1: One patient was lost to follow-up post dose 1 vaccination, overall participants is therefore 8 for this arm Arm 3: One patient withdrew from the study due to symptoms post dose 1 vaccination, overall participants is therefore 9 for this arm

Arm/Group Title	10 μg S. Flexneri 2a Invaplex	50 μg S. Flexneri 2a Invaplex	250 μg S. Flexneri 2a Invaplex	500 μg S. Flexneri 2a Invaplex
Arm/Group Description	8 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.	10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.
Measure Participants	8	9	9	10
ALS IgG (Invaplex)	1.2	8.6	9.3	7.0
ALS IgA (Invaplex)	1.3	8.6	3.7	4.3
ALS IgG (LPS)	1.2	2.9	4.0	3.5
ALS IgA (LPS)	1.1	3.2	2.0	2.1

Adverse Events

Time Frame	Through study completion, an average of 8 months
Adverse Event Reporting Description	Vaccine-related (possibly, probably, definitely) surveyed signs and symptoms of all study subjects receiving at least one dose of investigational product was assessed through targeted physical exams, symptom surveys, and other adverse events (AE) monitoring. Subjects were observed in clinic for 30 minutes, 24 hours, and 7days post vaccination to review their symptom diaries and to report any AEs. All vaccine-related and unrelated (not related, unlikely) AEs were reported.
Arm/Group Title	10 μg S. Flexneri 2a Invaplex		50 μg S. Flexneri 2a Invaplex		250 μg S. Flexneri 2a Invaplex		500 μg S. Flexneri 2a Invaplex
Arm/Group Description	9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.		9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.		10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.		10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: 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.
All Cause Mortality
	10 μg S. Flexneri 2a Invaplex		50 μg S. Flexneri 2a Invaplex		250 μg S. Flexneri 2a Invaplex		500 μg S. Flexneri 2a Invaplex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)
Serious Adverse Events
	10 μg S. Flexneri 2a Invaplex		50 μg S. Flexneri 2a Invaplex		250 μg S. Flexneri 2a Invaplex		500 μg S. Flexneri 2a Invaplex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	10 μg S. Flexneri 2a Invaplex		50 μg S. Flexneri 2a Invaplex		250 μg S. Flexneri 2a Invaplex		500 μg S. Flexneri 2a Invaplex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/9 (100%)		9/9 (100%)		10/10 (100%)		10/10 (100%)
Blood and lymphatic system disorders
Leukocytosis	0/9 (0%)		0/9 (0%)		0/10 (0%)		2/10 (20%)
Hemoglobinemia	1/9 (11.1%)		0/9 (0%)		0/10 (0%)		0/10 (0%)
Leukopenia	0/9 (0%)		0/9 (0%)		2/10 (20%)		0/10 (0%)
Lymphocytopenia	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)
Cardiac disorders
Bradycardia	1/9 (11.1%)		0/9 (0%)		0/10 (0%)		2/10 (20%)
Tachycardia	0/9 (0%)		1/9 (11.1%)		0/10 (0%)		0/10 (0%)
Eye disorders
Itchy Eyes	0/9 (0%)		2/9 (22.2%)		0/10 (0%)		3/10 (30%)
Tearing Eyes	0/9 (0%)		1/9 (11.1%)		0/10 (0%)		0/10 (0%)
Gastrointestinal disorders
Abdominal Cramps	0/9 (0%)		0/9 (0%)		0/10 (0%)		1/10 (10%)
Abdominal Discomfort	1/9 (11.1%)		0/9 (0%)		0/10 (0%)		0/10 (0%)
Diarrhoea	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)
Dry Chapped Lips	0/9 (0%)		0/9 (0%)		0/10 (0%)		1/10 (10%)
Loose Stools	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)
Nausea	0/9 (0%)		0/9 (0%)		0/10 (0%)		1/10 (10%)
General disorders
Fatigue	3/9 (33.3%)		2/9 (22.2%)		2/10 (20%)		4/10 (40%)
Fever	1/9 (11.1%)		0/9 (0%)		1/10 (10%)		1/10 (10%)
Chest Tightness (Unknown Etiology)	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)
Infections and infestations
Pharyngitis	3/9 (33.3%)		1/9 (11.1%)		4/10 (40%)		7/10 (70%)
Right Upper Lip Fever Blister	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)
Sinusitis	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)
Urinary Tract Infection (UTI)	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)
Investigations
AST Elevation	0/9 (0%)		0/9 (0%)		2/10 (20%)		1/10 (10%)
BUN Elevation	0/9 (0%)		0/9 (0%)		0/10 (0%)		1/10 (10%)
Low Hemoglobin	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)
Metabolism and nutrition disorders
Dehydration	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)
Hypernatremia	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)
Hypoglycemia	0/9 (0%)		0/9 (0%)		1/10 (10%)		2/10 (20%)
Musculoskeletal and connective tissue disorders
Myalgia	1/9 (11.1%)		0/9 (0%)		2/10 (20%)		2/10 (20%)
Arthralgia	0/9 (0%)		0/9 (0%)		0/10 (0%)		1/10 (10%)
Back Pain	1/9 (11.1%)		0/9 (0%)		0/10 (0%)		0/10 (0%)
Joint Aches (Left Knee and Left Elbow)	0/9 (0%)		0/9 (0%)		0/10 (0%)		1/10 (10%)
Olecranon bursitis	0/9 (0%)		1/9 (11.1%)		0/10 (0%)		0/10 (0%)
Right Hip Tendonitis	0/9 (0%)		0/9 (0%)		0/10 (0%)		1/10 (10%)
Right Knee Pain	0/9 (0%)		1/9 (11.1%)		0/10 (0%)		0/10 (0%)
Nervous system disorders
Headache	3/9 (33.3%)		2/9 (22.2%)		4/10 (40%)		5/10 (50%)
Lightheadedness	1/9 (11.1%)		0/9 (0%)		0/10 (0%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/9 (11.1%)		1/9 (11.1%)		1/10 (10%)		3/10 (30%)
Epistaxis	0/9 (0%)		7/9 (77.8%)		4/10 (40%)		3/10 (30%)
Nasal Burning	1/9 (11.1%)		2/9 (22.2%)		0/10 (0%)		0/10 (0%)
Nasal Congestion	6/9 (66.7%)		5/9 (55.6%)		6/10 (60%)		10/10 (100%)
Nasal Itching	1/9 (11.1%)		4/9 (44.4%)		1/10 (10%)		2/10 (20%)
Nasal Mucosal Hyperemia	2/9 (22.2%)		1/9 (11.1%)		6/10 (60%)		2/10 (20%)
Nasal Pain	0/9 (0%)		1/9 (11.1%)		0/10 (0%)		0/10 (0%)
Nasal Stuffiness	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)
Nasal Tenderness	2/9 (22.2%)		1/9 (11.1%)		3/10 (30%)		4/10 (40%)
Post-Nasal Drip	2/9 (22.2%)		4/9 (44.4%)		6/10 (60%)		9/10 (90%)
Pulmonary Irritation	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)
Rhinorrhea	4/9 (44.4%)		5/9 (55.6%)		7/10 (70%)		6/10 (60%)
Sinus Pain	0/9 (0%)		3/9 (33.3%)		0/10 (0%)		2/10 (20%)
Sneezing	4/9 (44.4%)		3/9 (33.3%)		5/10 (50%)		5/10 (50%)
Upper Respiratory Infection (URI)	1/9 (11.1%)		1/9 (11.1%)		1/10 (10%)		2/10 (20%)
Nasal Ulcer	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)
Pleuritic pain	1/9 (11.1%)		0/9 (0%)		0/10 (0%)		0/10 (0%)
Vascular disorders
Hypertension	0/9 (0%)		1/9 (11.1%)		0/10 (0%)		0/10 (0%)
Systolic Hypertension	0/9 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.