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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
103
Icddr,B
Dhaka, Bangladesh
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.
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.
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.
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.
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.
Time frame: 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.
Time frame: SAEs at any time and AEs after any vaccination until Day 168 (Cohort A1, B1) and Day 224 (all other Cohorts).
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.
Time frame: 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.
Time frame: 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..
Time frame: Day 63
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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.
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: At any time (Day 0 to Day 84)