DiarrheaNCT01813071
Safety Study of Live Attenuated Oral Shigella (WRSS1) Vaccine in Bangladeshi Adults and Children
A study testing WRSS1 in people with Diarrhea, run by PATH at 1 site in Bangladesh.
Trial summary
This is a research study about an experimental (investigational) oral Shigella sonnei - Walter Reed S. sonnei (WRSS1). WRSS1 is a live vaccine that is being made to prevent disease from Shigella, which causes bloody, watery diarrhea. Read more about this study
- Who is it for?
- Ages 5 to 39 yearsHealthy volunteers can take part
- Conditions the study is for
- Diarrhea
- What is being tested?
- WRSS1
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 1 siteBangladesh
- Study dates
- Aug 2013to Apr 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 39 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Healthy male or female adults from 18-39 years old, inclusive
- General good health as determined by the screening evaluation no greater than 30 days before admission
- Properly informed about the study, able to understand it and sign the informed consent form
- Normal bowel habits (< 3 grade 1 or 2 stools each day; ≥ 1 grade 1 or 2 stools every 2 days)
- Free of obvious health problems as established by medical history and clinical examination before entering into the study.
- Available for the entire period of the study and reachable by study staff throughout the entire follow-up period
- Females of childbearing potential who are willing to take a serum pregnancy test at screening and urine pregnancy tests before each vaccination. Pregnancy tests must be negative before each vaccination. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is also acceptable.
- Signed Informed Consent
Who cannot join
- Presence of a significant medical or psychiatric condition that in the opinion of the Investigator precludes participation in the study
- Known infection with Hepatitis C or Human Immunodeficiency Virus (HIV)
- History of congenital abdominal disorders, intussusception, abdominal surgery or any other congenital disorder.
- Participation in research involving another investigational product (defined as receipt of investigational product) 30 days before planned date of first vaccination or concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational product
- Clinically significant abnormalities on physical examination
- Clinically significant abnormalities in screening hematology, serum chemistry, or urinalysis as determined by the PI or the PI in consultation with the Study Physician
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- History of febrile illness within 48 hours prior to vaccination
- Known or suspected impairment of immunological function based on medical history and physical examination
- Prior receipt of any Shigella vaccine
- Fever at the time of immunization. Fever is defined as a temperature ≥ 37.5 degrees Celsius (99.5 degrees Fahrenheit) on axillary, oral, or tympanic measurement
- Clinical evidence of active gastrointestinal illness
- Prior receipt of a blood transfusion or blood products, including immunoglobulins
- Presence of any significant systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination which would endanger the participant's health or is likely to result in non-conformance to the protocol.
- History of any neurologic disorders or seizures.
- Acute disease at the time of enrolment
- Evidence of current excessive alcohol consumption
- Evidence of current illicit drug use or drug dependence
- Current use of iron or zinc supplements within the past 7 days; current use of antacids (Histamine H2-receptor antagonists (H2 blockers), Omeprazole, over the counter (OTC) agents) or immunosuppressive drug
- Allergy to quinolone, sulfa, and penicillin classes of antibiotics
- History of any of the following conditions within the past 10 years:
- Arthritis (two or more episodes of joint pain and swelling)
- Gastrointestinal disease (diagnosed by a doctor as having irritable bowel disease, Crohn's disease, ulcerative colitis (biopsy confirmed), celiac disease, stomach or intestinal ulcers
- Dyspepsia (indigestion or heartburn requiring medication more than once per week)
- History of gallbladder disease
- History of chronic heart disease
- Any conditions which, in the opinion of the investigator, might jeopardize the safety of study participants or interfere with the evaluation of the study objectives
- Receipt of antimicrobial drugs for any reason or a fever ≥ 38 degrees Celsius within 7 days before vaccination
- History of diarrhea during the 7 days before vaccination.
- Has any household member(s) who is immunocompromised or under the age of 2 years old.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blinded, Placebo-controlled, Dose-Escalation, Age-Descending Study to Assess the Safety and Tolerability of Live Attenuated, Oral Shigella WRSS1 (Walter Reed S. Sonnei) Vaccine in Bangladeshi Adults and Children
This is a research study about an experimental (investigational) oral Shigella sonnei - Walter Reed S. sonnei (WRSS1). WRSS1 is a live vaccine that is being made to prevent disease from Shigella, which causes bloody, watery diarrhea. Infants and children living in developing countries experience the greatest consequences of this disease. The purpose of this study is to find a dose of the vaccine that is safe, tolerable, and develops an immune response. About 39 healthy adults, ages 18-39, and 48 healthy children, ages 5-9, will participate in this study. Once the vaccine is proven safe and tolerable in adults, then it will be tested in the children. This study will require volunteers to stay in the research facility for several nights for the first dose; they will not be required to stay overnight for the second and third doses. Participants will be assigned to receive 1 of 3 vaccine dose levels by mouth. Study procedures include: stool samples, blood samples and documenting side effects. Participants will be involved in study related procedures for about 8 months.
Read the detailed description
This is a single site, double-blind, randomized, placebo-controlled, dose-escalation, age-descending study that will start testing the vaccine in healthy adults and move subsequently into school-age children. The study is designed as 2 parts, each part comprising 3 cohorts. The cohort receiving the lowest dose in Parts A and B will receive only one administration of vaccine or placebo; the subsequent two higher dose cohorts in Parts A and B will receive three administrations of vaccine or placebo. In each cohort, the first dose and immediate safety evaluation will be conducted at the International Centre for Diarrhoeal Disease Research (icddr,b) Inpatient Unit, where the participants will be admitted for observation for 72 hours. Follow-up visits for participants in A1 and B1 will take place on an outpatient basis at the Mirpur, Bangladesh (Mirpur) Field Office. Second and third vaccinations within A2, A3, B2, and B3 cohorts and all follow-up visits will take place on an outpatient basis at the Mirpur Field Office. Before enrolling participants in subsequent cohorts to receive a higher vaccine dose, or to move to the lower age group, the safety data from the previous cohort(s) (through Study Day 7) will be evaluated and reviewed by the Internal Protocol Safety Team (IPST) comprised of the study physician, the Medical Monitor from GVK Biosciences (GVK), the principal investigator, and the Medical Monitor from PATH Vaccine Solutions (PVS). Upon completion of the last adult cohort, the Data Safety Monitoring Board (DSMB -an advisory body to the Ethical Review Committee) will convene to review the cumulative safety data and IPST recommendation, and determine whether to proceed to Part B (children). Adverse events (AE)s will be graded according to standardized criteria. The immunogenicity outcome measures of interest include serum immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies by Antibodies in Lymphocyte Supernatant (ALS) assay against S. sonnei2a lipopolysaccharide (LPS), shedding profile of WRSS1, and vaccine-specific mucosal IgA responses.
The proposed study builds upon successful preliminary observations with this vaccine in the US, Israel and Thailand. While secondary objectives include studying the immunogenicity of the WRSS1 vaccine, the primary goal of the current trial is to establish a clear safety profile for the WRSS1 vaccine in adults and children 5-9 years old.The primary objective of the study is to evaluate the safety and tolerability of the vaccine; the secondary objective is to evaluate vaccine immunogenicity.
- Conditions
- Diarrhea
- Being tested
- WRSS1
- Keywords
- Enterobacteriaceae Infections, Gram-Negative Bacterial Infections, Bacterial Infections, Gastroenteritis, Gastrointestinal Diseases, Digestive System Diseases, Intestinal Diseases, Shigellosis
- Medical subject headings
- Diarrhea, Enterobacteriaceae Infections, Gram-Negative Bacterial Infections, Bacterial Infections, Gastroenteritis, Gastrointestinal Diseases, Digestive System Diseases, Intestinal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WRSS1Biological
| Study group | Role | What they receive |
|---|---|---|
| Part A (Adults): Cohort A1 | Experimental | One oral dose of ~3x10^4 cfu WRSS1(10 participants) or placebo (3 participants) Receives: Biological: WRSS1 |
| Part A (Adults): Cohort A2 | Experimental | Three oral doses of ~3x10^5 cfu WRSS1(10 participants) or placebo (3 participants) Receives: Biological: WRSS1 |
| Part A (Adults): Cohort A3 | Experimental | Three oral doses of ~3x10^6 cfu WRSS1(10 participants) or placebo (3 participants) Receives: Biological: WRSS1 |
| Part B (Children): Cohort B1 | Experimental | One oral dose of ~3x10^3 cfu WRSS1(12 participants) or placebo (4 participants) Receives: Biological: WRSS1 |
| Part B (Children): Cohort B2 | Experimental | Three oral doses of ~3x10^4 cfu WRSS1(12 participants) or placebo (4 participants) Receives: Biological: WRSS1 |
| Part B (Children): Cohort B3 | Experimental | Three oral doses of ~3x10^5 cfu WRSS1(12 participants) or placebo (4 participants) Receives: Biological: WRSS1 |
| Part B (Children): Cohort B4 | Experimental | Three oral doses of ~3x10^6 cfu WRSS1(12 participants) or placebo (4 participants) Receives: Biological: WRSS1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and Percentage of Participants With Serious Adverse Events (SAEs)
Based on maximum severity per participant over all serious adverse events (SAEs) within 6 months of any vaccination. A Serious Adverse Event, including serious suspected adverse reaction or serious adverse reaction as determined by the Investigator or the sponsor, was any event that results in any of the following outcomes: Inpatient hospitalization or prolongation of existing hospitalization , life-threatening AE that in the opinion of the investigator or sponsor put the participant at immediate risk of death, persistent or significant incapacity or substantial disruption, congenital abnormality or birth defect, a medically important event that may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed or death.
Measured: Day -1(admission day) through 6 months (Day 224 +/- 14 days) after the third vaccination for Cohorts A2,A3, B2, B3, B4, and after the first vaccination (Day 168 +/- 14 days) for Cohorts A1 and B1.
Number and Percentage of Participants With Any Non-serious Unsolicited Adverse Events
Based on subject count over all non-serious adverse events. An Adverse event was defined as any untoward medical occurrence in humans, whether or not considered drug related, that occurred during the conduct of a clinical trial. Any change in clinical status, ECGs, routine labs, x-rays, physical examinations, etc., that was considered clinically significant by the study investigator, was considered an AE. This definition also included an exacerbation or worsening of pre-existing conditions or events, inter-current illnesses, injuries, or vaccine or drug interaction, or worsening of abnormal clinical laboratory values. All AEs were assessed by the clinician using a protocol defined grading system.
Measured: Day -1(admission day) through 6 months (Day 224 +/- 14 days) after the third vaccination for Cohorts A2,A3, B2, B3, B4, and after the first vaccination (Day 168 +/- 14 days) for Cohorts A1 and B1.
Number and Percentage of Participants With Solicited Systemic and Intestinal Reactions
Maximum severity per participant of any systemic or any gastrointestinal reactogenicity recorded within 7 days of any vaccination is reported. Solicited Systemic reactogenicity events assessed included fever, headache, malaise, generalized myalgia, arthralgia, chills, reactive arthritis and decreased appetite. Intestinal solicited reactogenicity events assessed included abdominal cramps, abdominal pain, nausea, vomiting, loose stool, diarrhea, dysentery, bloating, excess flatulence and constipation. Diarrhea and dysentery were assessed both during inpatient (first three day period post-vaccination) and outpatient ( post-vaccination days 4-7) periods post-vaccination 1. Vaccinations 2 and 3 did not have an inpatient admission period for any participants. Diarrhea severity was determined on the basis of stool number, grading and stool weight during the inpatient period and by stool number and grading only during the outpatient period.
Measured: Day 0 through Day 7 after any vaccination
Number and Percentage of Participants With Any Unsolicited AEs and SAEs Judged as Having a Reasonable Possibility That the Study Product Caused the Event
Adverse event (AE) was defined as any untoward medical occurrence in humans, whether or not considered drug related, that occurs during the conduct of a clinical trial. A Serious Adverse Event (SAE) , including serious suspected adverse reaction or serious adverse reaction as determined by the Investigator or the sponsor, was any event that results in any of the following outcomes: Inpatient hospitalization or prolongation of existing hospitalization , life-threatening AE that in the opinion of the investigator or sponsor put the participant at immediate risk of death, persistent or significant incapacity or substantial disruption, congenital abnormality or birth defect, a medically important event that may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed or death. Causality of the AE/SAE to the study drug was assessed by the Investigator as reasonable possibility that the study product caused the reported event.
Measured: SAEs at any time and AEs after any vaccination until Day 168 (Cohort A1, B1) and Day 224 (all other Cohorts).
Secondary outcomes (55)
Number and Percentage of Participants With a 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Titers in Lymphocyte Supernatant (ALS)
The mucosal immune response to WRSS1 was evaluated by assessing specific immunoglobulin A (IgA) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and a novel composition comprising invasin proteins and LPS from gram-negative bacteria (Invaplex) using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine LPS- and Invaplex-specific IgA responses from circulating lymphocytes. Proportion of participants with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 7
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in ALS
The mucosal immune response to WRSS1 was evaluated by assessing specific IgA (immunoglobulin A) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine LPS- and Invaplex-specific IgA responses from circulating lymphocytes. Proportion of participants with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 35
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in ALS
The mucosal immune response to WRSS1 was evaluated by assessing specific IgA (immunoglobulin A) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine LPS- and Invaplex-specific IgA responses from circulating lymphocytes. Proportion of participants with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer..
Measured: Day 63
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in ALS
The mucosal immune response to WRSS1 was evaluated by assessing specific IgA (immunoglobulin A) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine LPS- and Invaplex-specific IgA responses from circulating lymphocytes. Proportion of participants with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: At any time (Day 7 to Day 63)
Number and Percentage of Participants With a 4-fold Rise From Baseline in Immunoglobulin G (IgG ) IgG Antibodies in ALS
The mucosal immune response to WRSS1 was evaluated by assessing specific immunoglobulin G (IgG ) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine LPS- and Invaplex-specific IgG responses from circulating lymphocytes. Proportion of participants with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 7
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in ALS
The mucosal immune response to WRSS1 was evaluated by assessing specific IgG (immunoglobulin G) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine LPS- and Invaplex-specific IgG responses from circulating lymphocytes. Proportion of participants with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 35
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in ALS: Invaplex
The mucosal immune response to WRSS1 was evaluated by assessing specific IgG (immunoglobulin G) antibody responses to S. sonnei 2a Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine Invaplex-specific IgG responses from circulating lymphocytes. Proportion of participants with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 63
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in ALS: Lipopolysaccharide (LPS)
The mucosal immune response to WRSS1 was evaluated by assessing specific IgG (immunoglobulin G) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine LPS-specific IgG responses from circulating lymphocytes. Proportion of participants with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 63
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in ALS
The mucosal immune response to WRSS1 was evaluated by assessing specific IgG (immunoglobulin G) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine LPS- and Invaplex-specific IgG responses from circulating lymphocytes. Proportion of participants with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: At any time (Day 7 to Day 63)
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in ALS
The mucosal immune response to WRSS1 was evaluated by assessing specific immunoglobulin M (IgM) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine LPS- and Invaplex-specific IgM responses from circulating lymphocytes. Proportion of children with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 7
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in ALS: Invaplex
The mucosal immune response to WRSS1 was evaluated by assessing specific IgM (immunoglobulin M) antibody responses to S. sonnei 2a Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine Invaplex-specific IgM responses from circulating lymphocytes. Proportion of children with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 35
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in ALS: LPS
The mucosal immune response to WRSS1 was evaluated by assessing specific IgM (immunoglobulin M) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine LPS- specific IgM responses from circulating lymphocytes. Proportion of children with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 35
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in ALS: Invaplex
The mucosal immune response to WRSS1 was evaluated by assessing specific IgM (immunoglobulin M) antibody responses to S. sonnei 2a Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine Invaplex-specific IgM responses from circulating lymphocytes. Proportion of children with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 63
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in ALS : LPS
The mucosal immune response to WRSS1 was evaluated by assessing specific IgM (immunoglobulin M) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine LPS-specific IgM responses from circulating lymphocytes. Proportion of children with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 63
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in ALS
The mucosal immune response to WRSS1 was evaluated by assessing specific IgM (immunoglobulin M) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days before and after vaccination to determine LPS- and Invaplex-specific IgM responses from circulating lymphocytes. Proportion of children with a >= 4-fold increase in antibody titer beyond baseline (mean + 3 standard deviation) was determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: At any time (Day 7 to Day 63)
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgA (immunoglobulin A) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 7
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgA (immunoglobulin A) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 28
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgA (immunoglobulin A) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 35
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgA (immunoglobulin A) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 56
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgA (immunoglobulin A) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 63
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgA (immunoglobulin A) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 84
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgA (immunoglobulin A) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: At any time (Day 7 to Day 84)
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgG (immunoglobulin G) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 7
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgG (immunoglobulin G) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 28
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgG (immunoglobulin G) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 35
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgG (immunoglobulin G) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 56
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgG (immunoglobulin G) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 63
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgG (immunoglobulin G) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 84
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgG (immunoglobulin G) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: At any time (Day 7 to Day 84)
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in (Immunoglobulin M) IgM Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgM (immunoglobulin M) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 7
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgM (immunoglobulin M) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 28
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgM (immunoglobulin M) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 35
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgM (immunoglobulin M) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 56
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgM (immunoglobulin M) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 63
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgM (immunoglobulin M) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: Day 84
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in Serum
The systemic immune response to WRSS1 was evaluated by assessing the IgM (immunoglobulin M) antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in serum samples at Days -1, 7, 28, 35, 56, 63 and 84. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. A ≥4-fold rise in serum antibody titers was considered significant. Fold rise is the ratio of follow-up titer/baseline titer. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.
Measured: At any time (Day 7 to Day 84)
Number and Percentage of Adult Participants With a 2-fold Rise From Baseline in IgA and IgG Antibodies in ASC
Antibody Secreting Cell (ASC) by ELISPOT assay responses for IgA (immunoglobulin A) and IgG (immunoglobulin B) ASCs specific for LPS (lipopolysaccharide) and Invaplex were determined at Days -1, 7, 35, and 63. 2-fold increases of LPS and Invaplex specific IgA and IgG in ASC beyond baseline mean + 3 Standard Deviation (SD) were determined. Positive response was ≥8 spots per 1 million peripheral blood mononuclear cells.
Measured: Day 7
Number and Percentage of Adult Participants With a 2-fold Rise From Baseline in IgA and IgG Antibodies in ASC
Antibody Secreting Cell (ASC) by ELISPOT assay responses for IgA (immunoglobulin A) and IgG (immunoglobulin B) ASCs specific for LPS (lipopolysaccharide) and Invaplex were determined at Days -1, 7, 35, and 63. 2-fold increases of LPS and Invaplex specific IgA and IgG in ASC beyond baseline mean + 3 Standard Deviation (SD) were determined. Positive response was ≥8 spots per 1 million peripheral blood mononuclear cells.
Measured: Day 35
Number and Percentage of Adult Participants With a 2-fold Rise From Baseline in IgA and IgG Antibodies in ASC
Antibody Secreting Cell (ASC) by ELISPOT assay responses for IgA (immunoglobulin A) and IgG (immunoglobulin B) ASCs specific for LPS (lipopolysaccharide) and Invaplex were determined at Days -1, 7, 35, and 63. 2-fold increases of LPS and Invaplex specific IgA and IgG in ASC beyond baseline mean + 3 Standard Deviation (SD) were determined. Positive response was ≥8 spots per 1 million peripheral blood mononuclear cells.
Measured: Day 63
Number and Percentage of Adult Participants With a 2-fold Rise From Baseline in IgA and IgG Antibodies in ASC
Antibody Secreting Cell (ASC) by ELISPOT assay responses for IgA (immunoglobulin A) and IgG (immunoglobulin B) ASCs specific for LPS (lipopolysaccharide) and Invaplex were determined at Days -1, 7, 35, and 63. 2-fold increases of LPS and Invaplex specific IgA and IgG in ASC beyond baseline mean + 3 Standard Deviation (SD) were determined. Positive response was ≥8 spots per 1 million peripheral blood mononuclear cells.
Measured: At any time (Day 7 to Day 63)
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Stool
The mucosal immune response to the WRSS1 was evaluated by assessing Fecal IgA (immunoglobulin A) antibody responses in stool to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in enzyme-linked immunosorbent assay (ELISA) assays, at Days -1, 7, 28, 35, 56, 63, and 84. 4-fold increases of LPS and invaplex-specific IgA in stool beyond baseline mean + 3 SD (standard deviation) were determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer. Pro-inflammatory cytokines (Interleukin 1 beta (IL-1β), Interleukin 8 (IL-8), tumor necrosis factor alpha (TNF-α) and Interferon gamma (IFN-γ)) were measured in stool extracts using commercially available ELISA kits.
Measured: Day 7
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Stool
The mucosal immune response to the WRSS1 was evaluated by assessing Fecal IgA (immunoglobulin A) antibody responses in stool to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in ELISA assays, at Days -1, 7, 28, 35, 56, 63, and 84. 4-fold increases of LPS and invaplex-specific IgA in stool beyond baseline mean + 3 SD (standard deviation) were determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer.Pro-inflammatory cytokines (IL-1β, IL-8, TNF-α and IFN-γ) were measured in stool extracts using commercially available ELISA kits.
Measured: Day 28
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Stool
The mucosal immune response to the WRSS1 was evaluated by assessing Fecal IgA (immunoglobulin A) antibody responses in stool to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in ELISA assays, at Days -1, 7, 28, 35, 56, 63, and 84. 4-fold increases of LPS and invaplex-specific IgA in stool beyond baseline mean + 3 SD (standard deviation) were determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer. Pro-inflammatory cytokines (IL-1β, IL-8, TNF-α and IFN-γ) were measured in stool extracts using commercially available ELISA kits.
Measured: Day 35
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Stool
The mucosal immune response to the WRSS1 was evaluated by assessing Fecal IgA (immunoglobulin A) antibody responses in stool to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in ELISA assays, at Days -1, 7, 28, 35, 56, 63, and 84. 4-fold increases of LPS and invaplex-specific IgA in stool beyond baseline mean + 3 SD (standard deviation) were determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer. Pro-inflammatory cytokines (IL-1β, IL-8, TNF-α and IFN-γ) were measured in stool extracts using commercially available ELISA kits.
Measured: Day 56
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Stool
The mucosal immune response to the WRSS1 was evaluated by assessing Fecal IgA (immunoglobulin A) antibody responses in stool to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in ELISA assays, at Days -1, 7, 28, 35, 56, 63, and 84. 4-fold increases of LPS and invaplex-specific IgA in stool beyond baseline mean + 3 SD (standard deviation) were determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer. Pro-inflammatory cytokines (IL-1β, IL-8, TNF-α and IFN-γ) were measured in stool extracts using commercially available ELISA kits.
Measured: Day 63
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Stool
The mucosal immune response to the WRSS1 was evaluated by assessing Fecal IgA (immunoglobulin A) antibody responses in stool to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in ELISA assays, at Days -1, 7, 28, 35, 56, 63, and 84. 4-fold increases of LPS and invaplex-specific IgA in stool beyond baseline mean + 3 SD (standard deviation) were determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer. Pro-inflammatory cytokines (IL-1β, IL-8, TNF-α and IFN-γ) were measured in stool extracts using commercially available ELISA kits.
Measured: Day 84
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Stool
The mucosal immune response to the WRSS1 was evaluated by assessing Fecal IgA (immunoglobulin A) antibody responses in stool to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in ELISA assays, at Days -1, 7, 28, 35, 56, 63, and 84. 4-fold increases of LPS and invaplex-specific IgA in stool beyond baseline mean + 3 SD (standard deviation) were determined. For those with a zero titer at baseline, fold-rise was defined as the follow-up titer. Pro-inflammatory cytokines (IL-1β, IL-8, TNF-α and IFN-γ) were measured in stool extracts using commercially available ELISA kits.
Measured: At any time (Day 7 to Day 84)
Number and Percentage of Participants With a 4-fold Rise From Baseline in Ratio of Specific IgA to Total IgA Antibodies in Stool
Fecal antibody responses were defined as a four-fold rise for specific IgA (immunoglobulin A) or a four-fold rise for the ratio of specific over total IgA at any time point after immunization. Fecal antibody response to the WRSS1 was evaluated by assessing Fecal IgA antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in ELISA assays at Days -1, 7, 28, 35, 56, 63, and 84 . For those participants with a zero titer at baseline fold-rise was defined as the follow-up titer.
Measured: Day 7
Number and Percentage of Participants With a 4-fold Rise From Baseline in Ratio of Specific IgA to Total IgA Antibodies in Stool
Fecal antibody responses were defined as a four-fold rise for specific IgA (immunoglobulin A) or a four-fold rise for the ratio of specific over total IgA at any time point after immunization. Fecal antibody response to the WRSS1 was evaluated by assessing Fecal IgA antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in ELISA assays at Days -1, 7, 28, 35, 56, 63, and 84 . For those participants with a zero titer at baseline fold-rise was defined as the follow-up titer.
Measured: Day 28
Number and Percentage of Participants With a 4-fold Rise From Baseline in Ratio of Specific IgA to Total IgA Antibodies in Stool
Fecal antibody responses were defined as a four-fold rise for specific IgA (immunoglobulin A) or a four-fold rise for the ratio of specific over total IgA at any time point after immunization. Fecal antibody response to the WRSS1 was evaluated by assessing Fecal IgA antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in ELISA assays at Days -1, 7, 28, 35, 56, 63, and 84 . For those participants with a zero titer at baseline fold-rise was defined as the follow-up titer.
Measured: Day 35
Number and Percentage of Participants With a 4-fold Rise From Baseline in Ratio of Specific IgA to Total IgA Antibodies in Stool
Fecal antibody responses were defined as a four-fold rise for specific IgA (immunoglobulin A) or a four-fold rise for the ratio of specific over total IgA at any time point after immunization. Fecal antibody response to the WRSS1 was evaluated by assessing Fecal IgA antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in ELISA assays at Days -1, 7, 28, 35, 56, 63, and 84 . For those participants with a zero titer at baseline fold-rise was defined as the follow-up titer.
Measured: Day 56
Number and Percentage of Participants With a 4-fold Rise From Baseline in Ratio of Specific IgA to Total IgA Antibodies in Stool
Fecal antibody responses were defined as a four-fold rise for specific IgA (immunoglobulin A) or a four-fold rise for the ratio of specific over total IgA at any time point after immunization. Fecal antibody response to the WRSS1 was evaluated by assessing Fecal IgA antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in ELISA assays at Days -1, 7, 28, 35, 56, 63, and 84 . For those participants with a zero titer at baseline fold-rise was defined as the follow-up titer.
Measured: Day 63
Number and Percentage of Participants With a 4-fold Rise From Baseline in Ratio of Specific IgA to Total IgA Antibodies in Stool
Fecal antibody responses were defined as a four-fold rise for specific IgA (immunoglobulin A) or a four-fold rise for the ratio of specific over total IgA at any time point after immunization. Fecal antibody response to the WRSS1 was evaluated by assessing Fecal IgA antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in ELISA assays at Days -1, 7, 28, 35, 56, 63, and 84 . For those participants with a zero titer at baseline fold-rise was defined as the follow-up titer.
Measured: Day 84
Number and Percentage of Participants With a 4-fold Rise From Baseline in Ratio of Specific IgA to Total IgA Antibodies in Stool
Fecal antibody responses were defined as a four-fold rise for specific IgA (immunoglobulin A) or a four-fold rise for the ratio of specific over total IgA at any time point after immunization. Fecal antibody response to the WRSS1 was evaluated by assessing Fecal IgA antibody responses to S. sonnei 2a LPS (lipopolysaccharide) and Invaplex in ELISA assays at Days -1, 7, 28, 35, 56, 63, and 84 . For those participants with a zero titer at baseline fold-rise was defined as the follow-up titer.
Measured: At any time (Day 7 to Day 84)
Number and Percentage of Adult Participants With WRSS1 Shedding at Any Time After Vaccination
Prevalence and distribution of vaccine shedding was determined by quantitative culture and polymerase chain reaction (PCR). The latter measured the mean relative abundance of microbiota by 16S ribosomal ribonucleic acid (rRNA) gene sequence analysis of stool at baseline and post-vaccination days. PCR and stool results were reported as positive if a positive result was reported at any time during the testing period.
Measured: At any time (Day 0 to Day 84)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2013 (estimated)
- Study startAug 2013
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DiarrheaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh
- Responsible party
- Sponsor
- Investigators
- Rubhana Raqib, PhD, Principal investigator, International Centre for Diarrhoeal Disease Research, Bangladesh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01813071
- Sponsor's protocol ID
- VAC 008
- Other IDs
- PR-12054
- Status last verified
- Feb 2019
- First submitted
- 14 Mar 2013
- Last updated
- 8 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Sarker P, Mily A, Ara A, Haque F, Maier N, Wierzba TF, Walker RI, Venkatesan MM, Raqib R. Functional Antibodies and Innate Immune Responses to WRSS1, a Live Oral Shigella sonnei Vaccine Candidate, in Bangladeshi Adults and Children. J Infect Dis. 2021 Dec 20;224(12 Suppl 2):S829-S839. doi: 10.1093/infdis/jiab395.
PubMed 34374425
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blinded, Placebo-controlled, Dose-Escalation, Age-Descending Study to Assess the Safety and Tolerability of Live Attenuated, Oral Shigella WRSS1 (Walter Reed S. Sonnei) Vaccine in Bangladeshi Adults and Children
- ClinicalTrials.gov ID
- NCT01813071
- Acronym / sponsor ID
- VAC 008
- Conditions
- Diarrhea
- Keywords
- Enterobacteriaceae Infections, Gram-Negative Bacterial Infections, Bacterial Infections, Gastroenteritis, Gastrointestinal Diseases, Digestive System Diseases, Intestinal Diseases, Shigellosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh
- Study start
- Aug 2013
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 18 Mar 2013 (estimated)
- Results
- Posted 8 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a research study about an experimental (investigational) oral Shigella sonnei - Walter Reed S. sonnei (WRSS1). WRSS1 is a live vaccine that is being made to prevent disease from Shigella, which causes bloody, watery diarrhea. Infants and children living in developing countries experience the greatest consequences of this disease. The purpose of this study is to find a dose of the vaccine that is safe, tolerable, and develops an immune response. About 39 healthy adults, ages 18-39, and 48 healthy children, ages 5-9, will participate in this study. Once the vaccine is proven safe and tolerable in adults, then it will be tested in the children. This study will require volunteers to stay in the research facility for several nights for the first dose; they will not be required to stay overnight for the second and third doses. Participants will be assigned to receive 1 of 3 vaccine dose levels by mouth. Study procedures include: stool samples, blood samples and documenting side effects. Participants will be involved in study related procedures for about 8 months.
Detailed description
This is a single site, double-blind, randomized, placebo-controlled, dose-escalation, age-descending study that will start testing the vaccine in healthy adults and move subsequently into school-age children. The study is designed as 2 parts, each part comprising 3 cohorts. The cohort receiving the lowest dose in Parts A and B will receive only one administration of vaccine or placebo; the subsequent two higher dose cohorts in Parts A and B will receive three administrations of vaccine or placebo. In each cohort, the first dose and immediate safety evaluation will be conducted at the International Centre for Diarrhoeal Disease Research (icddr,b) Inpatient Unit, where the participants will be admitted for observation for 72 hours. Follow-up visits for participants in A1 and B1 will take place on an outpatient basis at the Mirpur, Bangladesh (Mirpur) Field Office. Second and third vaccinations within A2, A3, B2, and B3 cohorts and all follow-up visits will take place on an outpatient basis at the Mirpur Field Office. Before enrolling participants in subsequent cohorts to receive a higher vaccine dose, or to move to the lower age group, the safety data from the previous cohort(s) (through Study Day 7) will be evaluated and reviewed by the Internal Protocol Safety Team (IPST) comprised of the study physician, the Medical Monitor from GVK Biosciences (GVK), the principal investigator, and the Medical Monitor from PATH Vaccine Solutions (PVS). Upon completion of the last adult cohort, the Data Safety Monitoring Board (DSMB -an advisory body to the Ethical Review Committee) will convene to review the cumulative safety data and IPST recommendation, and determine whether to proceed to Part B (children). Adverse events (AE)s will be graded according to standardized criteria. The immunogenicity outcome measures of interest include serum immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies by Antibodies in Lymphocyte Supernatant (ALS) assay against S. sonnei2a lipopolysaccharide (LPS), shedding profile of WRSS1, and vaccine-specific mucosal IgA responses.
The proposed study builds upon successful preliminary observations with this vaccine in the US, Israel and Thailand. While secondary objectives include studying the immunogenicity of the WRSS1 vaccine, the primary goal of the current trial is to establish a clear safety profile for the WRSS1 vaccine in adults and children 5-9 years old.The primary objective of the study is to evaluate the safety and tolerability of the vaccine; the secondary objective is to evaluate vaccine immunogenicity.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Part A (Adults): Cohort A1 | Experimental | Biological: WRSS1One oral dose of ~3x10^4 cfu WRSS1(10 participants) or placebo (3 participants) |
| Part A (Adults): Cohort A2 | Experimental | Biological: WRSS1Three oral doses of ~3x10^5 cfu WRSS1(10 participants) or placebo (3 participants) |
| Part A (Adults): Cohort A3 | Experimental | Biological: WRSS1Three oral doses of ~3x10^6 cfu WRSS1(10 participants) or placebo (3 participants) |
| Part B (Children): Cohort B1 | Experimental | Biological: WRSS1One oral dose of ~3x10^3 cfu WRSS1(12 participants) or placebo (4 participants) |
| Part B (Children): Cohort B2 | Experimental | Biological: WRSS1Three oral doses of ~3x10^4 cfu WRSS1(12 participants) or placebo (4 participants) |
| Part B (Children): Cohort B3 | Experimental | Biological: WRSS1Three oral doses of ~3x10^5 cfu WRSS1(12 participants) or placebo (4 participants) |
| Part B (Children): Cohort B4 | Experimental | Biological: WRSS1Three oral doses of ~3x10^6 cfu WRSS1(12 participants) or placebo (4 participants) |
Who may qualify
- Ages
- 5 to 39 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Healthy male or female adults from 18-39 years old, inclusive
- General good health as determined by the screening evaluation no greater than 30 days before admission
- Properly informed about the study, able to understand it and sign the informed consent form
- Normal bowel habits (< 3 grade 1 or 2 stools each day; ≥ 1 grade 1 or 2 stools every 2 days)
- Free of obvious health problems as established by medical history and clinical examination before entering into the study.
Key exclusion criteria (29 listed)
- Presence of a significant medical or psychiatric condition that in the opinion of the Investigator precludes participation in the study
- Known infection with Hepatitis C or Human Immunodeficiency Virus (HIV)
- History of congenital abdominal disorders, intussusception, abdominal surgery or any other congenital disorder.
- Participation in research involving another investigational product (defined as receipt of investigational product) 30 days before planned date of first vaccination or concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational product
- Clinically significant abnormalities on physical examination
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| WRSS1 | Biological | Part A (Adults): Cohort A1, Part A (Adults): Cohort A2, Part A (Adults): Cohort A3, Part B (Children): Cohort B1, Part B (Children): Cohort B2, Part B (Children): Cohort B3, Part B (Children): Cohort B4 |
Primary outcome
Number and Percentage of Participants With Serious Adverse Events (SAEs)
Time frame: Day -1(admission day) through 6 months (Day 224 +/- 14 days) after the third vaccination for Cohorts A2,A3, B2, B3, B4, and after the first vaccination (Day 168 +/- 14 days) for Cohorts A1 and B1.
Based on maximum severity per participant over all serious adverse events (SAEs) within 6 months of any vaccination. A Serious Adverse Event, including serious suspected adverse reaction or serious adverse reaction as determined by the Investigator or the sponsor, was any event that results in any of the following outcomes: Inpatient hospitalization or prolongation of existing hospitalization , life-threatening AE that in the opinion of the investigator or sponsor put the participant at immediate risk of death, persistent or significant incapacity or substantial disruption, congenital abnormality or birth defect, a medically important event that may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed or death.
Number and Percentage of Participants With Any Non-serious Unsolicited Adverse Events
Time frame: Day -1(admission day) through 6 months (Day 224 +/- 14 days) after the third vaccination for Cohorts A2,A3, B2, B3, B4, and after the first vaccination (Day 168 +/- 14 days) for Cohorts A1 and B1.
Based on subject count over all non-serious adverse events. An Adverse event was defined as any untoward medical occurrence in humans, whether or not considered drug related, that occurred during the conduct of a clinical trial. Any change in clinical status, ECGs, routine labs, x-rays, physical examinations, etc., that was considered clinically significant by the study investigator, was considered an AE. This definition also included an exacerbation or worsening of pre-existing conditions or events, inter-current illnesses, injuries, or vaccine or drug interaction, or worsening of abnormal clinical laboratory values. All AEs were assessed by the clinician using a protocol defined grading system.
Number and Percentage of Participants With Solicited Systemic and Intestinal Reactions
Time frame: Day 0 through Day 7 after any vaccination
Maximum severity per participant of any systemic or any gastrointestinal reactogenicity recorded within 7 days of any vaccination is reported. Solicited Systemic reactogenicity events assessed included fever, headache, malaise, generalized myalgia, arthralgia, chills, reactive arthritis and decreased appetite. Intestinal solicited reactogenicity events assessed included abdominal cramps, abdominal pain, nausea, vomiting, loose stool, diarrhea, dysentery, bloating, excess flatulence and constipation. Diarrhea and dysentery were assessed both during inpatient (first three day period post-vaccination) and outpatient ( post-vaccination days 4-7) periods post-vaccination 1. Vaccinations 2 and 3 did not have an inpatient admission period for any participants. Diarrhea severity was determined on the basis of stool number, grading and stool weight during the inpatient period and by stool number and grading only during the outpatient period.
Number and Percentage of Participants With Any Unsolicited AEs and SAEs Judged as Having a Reasonable Possibility That the Study Product Caused the Event
Time frame: SAEs at any time and AEs after any vaccination until Day 168 (Cohort A1, B1) and Day 224 (all other Cohorts).
Adverse event (AE) was defined as any untoward medical occurrence in humans, whether or not considered drug related, that occurs during the conduct of a clinical trial. A Serious Adverse Event (SAE) , including serious suspected adverse reaction or serious adverse reaction as determined by the Investigator or the sponsor, was any event that results in any of the following outcomes: Inpatient hospitalization or prolongation of existing hospitalization , life-threatening AE that in the opinion of the investigator or sponsor put the participant at immediate risk of death, persistent or significant incapacity or substantial disruption, congenital abnormality or birth defect, a medically important event that may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed or death. Causality of the AE/SAE to the study drug was assessed by the Investigator as reasonable possibility that the study product caused the reported event.
55 secondary outcomes
Number and Percentage of Participants With a 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Titers in Lymphocyte Supernatant (ALS)
Time frame: Day 7
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in ALS
Time frame: Day 35
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in ALS
Time frame: Day 63
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in ALS
Time frame: At any time (Day 7 to Day 63)
Number and Percentage of Participants With a 4-fold Rise From Baseline in Immunoglobulin G (IgG ) IgG Antibodies in ALS
Time frame: Day 7
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in ALS
Time frame: Day 35
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in ALS: Invaplex
Time frame: Day 63
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in ALS: Lipopolysaccharide (LPS)
Time frame: Day 63
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in ALS
Time frame: At any time (Day 7 to Day 63)
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in ALS
Time frame: Day 7
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in ALS: Invaplex
Time frame: Day 35
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in ALS: LPS
Time frame: Day 35
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in ALS: Invaplex
Time frame: Day 63
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in ALS : LPS
Time frame: Day 63
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in ALS
Time frame: At any time (Day 7 to Day 63)
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
Time frame: Day 7
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
Time frame: Day 28
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
Time frame: Day 35
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
Time frame: Day 56
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
Time frame: Day 63
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
Time frame: Day 84
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgA Antibodies in Serum
Time frame: At any time (Day 7 to Day 84)
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
Time frame: Day 7
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
Time frame: Day 28
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
Time frame: Day 35
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
Time frame: Day 56
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
Time frame: Day 63
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
Time frame: Day 84
Number and Percentage of Participants With a 4-fold Rise From Baseline in IgG Antibodies in Serum
Time frame: At any time (Day 7 to Day 84)
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in (Immunoglobulin M) IgM Antibodies in Serum
Time frame: Day 7
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in Serum
Time frame: Day 28
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in Serum
Time frame: Day 35
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in Serum
Time frame: Day 56
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in Serum
Time frame: Day 63
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in Serum
Time frame: Day 84
Number and Percentage of Child Participants With a 4-fold Rise From Baseline in IgM Antibodies in Serum
Time frame: At any time (Day 7 to Day 84)
Number and Percentage of Adult Participants With a 2-fold Rise From Baseline in IgA and IgG Antibodies in ASC
Time frame: Day 7
Number and Percentage of Adult Participants With a 2-fold Rise From Baseline in IgA and IgG Antibodies in ASC
Time frame: Day 35
Number and Percentage of Adult Participants With a 2-fold Rise From Baseline in IgA and IgG Antibodies in ASC
Time frame: Day 63
Number and Percentage of Adult Participants With a 2-fold Rise From Baseline in IgA and IgG Antibodies in ASC
Time frame: At any time (Day 7 to Day 63)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34374425Sarker P, Mily A, Ara A, Haque F, Maier N, Wierzba TF, Walker RI, Venkatesan MM, Raqib R. Functional Antibodies and Innate Immune Responses to WRSS1, a Live Oral Shigella sonnei Vaccine Candidate, in Bangladeshi Adults and Children. J Infect Dis. 2021 Dec 20;224(12 Suppl 2):S829-S839. doi: 10.1093/infdis/jiab395.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rubhana Raqib, PhD principal investigator
International Centre for Diarrhoeal Disease Research, Bangladesh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing WRSS1 in people with Diarrhea, run by PATH at 1 site in Bangladesh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bangladesh. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and Percentage of Participants With Serious Adverse Events (SAEs) (time frame: Day -1(admission day) through 6 months (Day 224 +/- 14 days) after the third vaccination for Cohorts A2,A3, B2, B3, B4, and after the first vaccination (Day 168 +/- 14 days) for Cohorts A1 and B1.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01813071, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2019.