SNPMiner Trials (Home Page)
Report for Mutation L460D
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 2 clinical trials
Clinical Trials
1 A Dose-Finding Study to Assess the Safety, Tolerability, and Immunogenicity of Inactivated Streptococcus Pneumoniae Whole Cell Vaccine Formulated With Alum (PATH-wSP) in Healthy Kenyan Young Adults and PCV-Primed Toddlers
The purpose of this study is to assess the safety and tolerability of PATH-wSP, administered intramuscularly to healthy Kenyan adults and toddlers who have been primed with a pneumococcal conjugate vaccine (PCV). Additionally, the study will explore whether a measurable immune response is elicited when PATH-wSP is administered to healthy Kenyan adults and toddlers who have been primed with PCV.
NCT02097472 Pneumonia, Pneumococcal Biological: PATH-wSP Biological: Synflorix Biological: Pentavac Other: Saline MeSH:Pneumonia, Pneumococcal Pneumonia
HPO:Pneumonia
Severity was defined in the protocol as grade 0-4 (none, mild, moderate, and severe).. Geometric Mean Concentrations (GMC) of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: ELISA Assay. --- L460D ---
Measured with enzyme-linked immunosorbent assay (ELISA).. Geometric Mean Concentrations (GMC) of IgG Antibodies Against L460D Pneumococcal Protein. --- L460D ---
Geometric Mean Fold Change of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: ELISA. --- L460D ---
Geometric Mean Fold Change of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: MSD. --- L460D ---
Fold Change in IgG Response to Pneumolysoid (L460D) Pneumococcal Protein Among Toddler Cohort (ELISA). --- L460D ---
Fold Change in IgG Response to L460D Pneumococcal Protein (MSD). --- L460D ---
Primary Outcomes
Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination.
Measure: Number/Percent of Adult Subjects Experiencing Fatigue/Malaise Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination.
Measure: Number/Percent of Adult Subjects Experiencing Myalgia Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Grade 2 includes repeated use of non-narcotic pain reliever for more than 24 hours.
Measure: Number/Percent of Adult Subjects Experiencing Headache Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Grade 2 includes use of non-narcotic pain reliever for more than 24 hours.
Measure: Number/Percent of Adult Subjects Experiencing Pain at Injection Site Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination.
Measure: Number/Percent of Adult Subjects Experiencing Tenderness at Injection Site Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Grade 1: does not interfere with activity Grade 2: interferes with activity
Measure: Number/Percent of Adult Subjects Experiencing Induration at Injection Site Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination.
Measure: Number/Percent of Adult Subjects Experiencing Fever at Injection Site Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination.
Measure: Number/Percent of Toddler Subjects Experiencing Fever Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Grade 2: includes diffuse macular/maculopapular/morbilliform rash
Measure: Number/Percent of Toddler Subjects Experiencing Cutaneous Rash Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Severity was defined in the protocol as grade 0-4 (none, mild, moderate, and severe).
Measure: Number/Percent of Toddler Subjects Experiencing Irritability Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Severity was defined in the protocol as grade 0-4 (none, mild, moderate, and severe).
Measure: Number/Percent of Toddler Subjects Experiencing Drowsiness Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Severity was defined in the protocol as grade 0-4 (none, mild, moderate, and severe).
Measure: Number/Percent of Toddler Subjects Experiencing Loss of Appetite Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination.
Measure: Number/Percent of Toddler Subjects Experiencing Pain/Tenderness at Injection Site Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Severity was defined in the protocol as grade 0-4 (none, mild, moderate, and severe).
Measure: Number/Percent of Toddler Subjects Experiencing Induration/Swelling at Injection Site Following Vaccination Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)Secondary Outcomes
Description: Measured with enzyme-linked immunosorbent assay (ELISA).
Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: ELISA Assay Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured with enzyme-linked immunosorbent assay (ELISA).
Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: ELISA Assay Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using meso scale discovery (MSD).
Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against L460D Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: Meso Scale Discovery (MSD) Assay Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)
Description: Measured using Meso Scale Discovery (MSD) Assay
Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against PhtD Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using Meso Scale Discovery (MSD) Assay
Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against BCH0785 Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using Meso Scale Discovery (MSD) Assay
Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against StkP Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using Meso Scale Discovery (MSD) Assay
Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against PcpA Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: MSD Assay
Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against SPWCA Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: MSD Assay
Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against PiuA Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: MSD Assay
Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against PiaA Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using ELISA
Measure: Geometric Mean Fold Change of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: ELISA Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using ELISA
Measure: Geometric Mean Fold Change of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: ELISA Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using MSD
Measure: Geometric Mean Fold Change of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: MSD Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using ELISA
Measure: Geometric Mean Fold Change of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: MSD Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using MSD
Measure: Geometric Mean Fold Change of IgG Antibodies Against PhtD Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using MSD
Measure: Geometric Mean Fold Change of IgG Antibodies Against BCH0785 Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using MSD
Measure: Geometric Mean Fold Change of IgG Antibodies Against StkP Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using MSD
Measure: Geometric Mean Fold Change of IgG Antibodies Against PcpA Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using MSD
Measure: Geometric Mean Fold Change of IgG Antibodies Against SPWCA Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using MSD
Measure: Geometric Mean Fold Change of IgG Antibodies Against PiuA Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using MSD
Measure: Geometric Mean Fold Change of IgG Antibodies Against PiaA Pneumococcal Protein Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Measured using ELISA
Measure: Fold Change in IgG Response to Pneumolysoid (L460D) Pneumococcal Protein Among Toddler Cohort (ELISA) Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)Description: Measured using ELISA
Measure: Fold Change in IgG Response to PspA-Fam1 (ELISA) Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)Description: Measured using MSD
Measure: Fold Change in IgG Response to L460D Pneumococcal Protein (MSD) Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)Description: Measured using MSD
Measure: Fold Change in IgG Response to PspA-Fam1 Pneumococcal Protein (MSD) Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)Description: Measured using MSD
Measure: Fold Change in IgG Response to PhtD Pneumococcal Protein Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)Description: Measured using MSD
Measure: Fold Change in IgG Response to BCH0785 Pneumococcal Protein Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)Description: Measured using MSD
Measure: Fold Change in IgG Response to StkP Pneumococcal Protein Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)Description: Measured using MSD
Measure: Fold Change in IgG Response to PcpA Pneumococcal Protein Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)Description: Measured using MSD
Measure: Fold Change in IgG Response to SPWCA Pneumococcal Protein Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)Description: Measured using MSD
Measure: Fold Change in IgG Response to PiuA Pneumococcal Protein Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)Description: Measured using MSD
Measure: Fold Change in IgG Response to PiaA Pneumococcal Protein Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)Description: Functional antibody responses to Ply (pneumolysin) were assessed using a toxin neutralization assay based on the ability of antibodies to neutralize wild-type Ply-induced lysis of rabbit red blood cells. Briefly, serial 2-fold dilutions (starting at 1/5 dilution) of human serum samples were added together with wild-type Ply in 96-well plates. Rabbit red blood cells were then added and following incubation supernatants removed and transferred to new 96-well plates and absorbance measured at 540 nm using a spectrophotometer plate reader. The mean A450 nm blank value was subtracted by 10% to obtain the Plate Specific Cut Point for each plate. Each sample was categorized as negative (<1/20) or positive (with titer between 1/20 and 1/320).
Measure: Number/Percentage of Adult Subjects With Neutralizing Antibody Response to Pneumolysin Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Description: Functional antibody responses to Ply (pneumolysin) were assessed using a toxin neutralization assay based on the ability of antibodies to neutralize wild-type Ply-induced lysis of rabbit red blood cells. Briefly, serial 2-fold dilutions (starting at 1/5 dilution) of human serum samples were added together with wild-type Ply in 96-well plates. Rabbit red blood cells were then added and following incubation supernatants removed and transferred to new 96-well plates and absorbance measured at 540 nm using a spectrophotometer plate reader. The mean A450 nm blank value was subtracted by 10% to obtain the Plate Specific Cut Point for each plate. Each sample was categorized as negative (<1/20) or positive (with titer between 1/20 and 1/320).
Measure: Number/Percentage of Toddler Subjects With Neutralizing Antibody Response to Pneumolysin Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)Other Outcomes
Description: GMCs of these IgG proteins were measured to assess potential interference of PATH-wSP with 10-valent pneumococcal conjugate vaccine (Synflorix). GMCs of Cohort 1 were measured at a different time point than those in Cohort 2, so results are presented separately.
Measure: Geometric Mean Concentration (GMCs) of PNC-IgG Serotypes Among Toddler Subjects Time: 12 weeks (Cohort 1) and 4 weeks (Cohort 2) post-vaccination 1Description: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.
Measure: Geometric Mean Concentration (GMC) Ratio of Diptheria Booster Immune Response Among Toddler Subjects Time: 12 weeks post vaccination 1Description: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.
Measure: Geometric Mean Concentration (GMC) Ratio of Hepatitis B Booster Immune Response Among Toddler Subjects Time: 12 weeks post vaccination 1Description: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.
Measure: Geometric Mean Concentration (GMC) Ratio of Haemophilus Influenzae Type b (Hib) Booster Immune Response Among Toddler Subjects Time: 12 weeks post vaccination 1Description: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.
Measure: Geometric Mean Concentration (GMC) Ratio of Pertussis FHA and Pertussis Toxin Immune Response Among Toddler Subjects Time: 12 weeks post vaccination 1Description: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.
Measure: Geometric Mean Concentration (GMC) Ratio of Pertussis Fimbriae Immune Response Among Toddler Subjects Time: 12 weeks post vaccination 1Description: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.
Measure: Geometric Mean Concentration (GMC) Ratio of Tetanus Booster Immune Response Among Toddler Subjects Time: 12 weeks post vaccination 12 A Prospective Study to Assess the Nasopharyngeal Carriage of Streptococcus Pneumoniae (SPn), Long Term Safety and Immune Persistence in Healthy Kenyan PCV-Primed Toddlers (12-15 Months of Age) Who Received a Whole Cell Pneumococcal Vaccine (PATH-wSP) Compared to Controls
This study evaluated the change in nasopharyngeal carriage (NPC) of Streptococcus pneumoniae (SPn), hypothesizing that it would be reduced post-vaccination with Streptococcus pneumoniae whole cell vaccine with aluminum hydroxide adjuvant (PATH-wSP) and that PATH-wSP would remain safe and well-tolerated over the course of the study.
NCT02146365 Pneumococcal Disease MeSH:Pneumococcal Infections
Immunogenicity was evaluated based on the following assays: Immunoglobulin (IgG) response to pneumolysoid [L460D] and pneumococcal surface protein A family 1 [PspA-Fam1] was measured by enzyme-linked immunosorbent assay (ELISA). --- L460D ---
IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA). --- L460D ---
Immunogenicity was evaluated based on the following assays: Immunoglobulin (IgG) response to pneumolysoid (L460D) and pneumococcal surface protein A family 1 (PspA-Fam1) was measured by enzyme-linked immunosorbent assay (ELISA). --- L460D ---
Immunogenicity was evaluated based on the following assays: IgG response to pneumolysoid [L460D] and pneumococcal surface protein A family 1 [PspA-Fam1] was measured by enzyme-linked immunosorbent assay (ELISA). --- L460D ---
IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA) The fold-change was calculated as the 6-month post-vaccination (Week 32) IgG response divided by the Baseline IgG response.. Percentage of Participants Meeting Seroresponse Fold-Rise Categories at 6 Months Post Vaccination 2. The percentage of participants with a seroresponse, defined as a ≥ 2, ≥ 3, and ≥ 4 fold-rise above Baseline in IgG antibody levels against Pneumococcal proteins. --- L460D ---
Primary Outcomes
Description: The prevalence of Streptococcus pneumoniae (SPn) in the nasopharynx was measured by the number (and percentage) of participants positive for SPn detected by quantitative polymerase chain reaction (qPCR) from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only plus non-interventional participants enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only plus non-interventional participants enrolled during Cohort 2
Measure: Prevalence of Streptococcus Pneumoniae in Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: The density of Streptococcus pneumoniae (SPn) in the nasopharynx was measured by the number of autolysin (LytA) gene copies detected by quantitative polymerase chain reaction (qPCR) from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Density of Streptococcus Pneumoniae in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Secondary Outcomes
Description: Immunogenicity was evaluated based on the following assays: Immunoglobulin (IgG) response to pneumolysoid [L460D] and pneumococcal surface protein A family 1 [PspA-Fam1] was measured by enzyme-linked immunosorbent assay (ELISA). IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA)
Measure: Geometric Mean Concentration (GMC) of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins Time: Baseline (Week 0), 4 weeks post-vaccination 2 (Week 12), and 6 months post-vaccination 2 (Week 32).Description: Data reported are the geometric mean concentration at 6 months post-vaccination 2 (Week 32) for each PATH-wSP group divided by the Booster (Synflorix and Pentavax)-only group (N=38). Immunogenicity was evaluated based on the following assays: Immunoglobulin (IgG) response to pneumolysoid (L460D) and pneumococcal surface protein A family 1 (PspA-Fam1) was measured by enzyme-linked immunosorbent assay (ELISA). IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA)
Measure: Geometric Mean Concentration Ratios of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins for PATH-wSP Groups Versus the Booster Only Group Time: Week 32Description: Immunogenicity was evaluated based on the following assays: IgG response to pneumolysoid [L460D] and pneumococcal surface protein A family 1 [PspA-Fam1] was measured by enzyme-linked immunosorbent assay (ELISA). IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA) The fold-change was calculated as the 6-month post-vaccination (Week 32) IgG response divided by the Baseline IgG response.
Measure: Geometric Mean Fold Change of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins Time: Baseline and Week 32Description: The percentage of participants with a seroresponse, defined as a ≥ 2, ≥ 3, and ≥ 4 fold-rise above Baseline in IgG antibody levels against Pneumococcal proteins. Fold-rise was calculated as the 6-month post-vaccination (Week 32) IgG response divided by the Baseline IgG level. Immunogenicity was evaluated based on the following assays: IgG response to pneumolysoid [L460D] and pneumococcal surface protein A family 1 [PspA-Fam1] was measured by enzyme-linked immunosorbent assay (ELISA). IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA)
Measure: Percentage of Participants Meeting Seroresponse Fold-Rise Categories at 6 Months Post Vaccination 2 Time: Baseline and Week 32Description: Neutralizing antibody responses to pneumolysin were assessed at Baseline and 6 months post vaccination 2 using an in vitro toxin neutralization assay that measures the ability of antibodies to neutralize wild-type pneumolysin-induced lysis of rabbit red blood cells. Each sample was categorized as negative (< 1/20 dilution) or positive (with titer between 1/20 and 1/320 dilution). Responses at higher dilutions indicate higher levels of neutralizing antibodies to pneumolysin.
Measure: Number of Participants With Neutralizing Antibody Response to Pneumolysin Time: Baseline (Week 0) and 6 months post-vaccination 2 (Week 32)Description: An AE was defined as any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or psychological/physiologic observations occurring in a person in a clinical study. The AEs collected in this non-interventional study were those that remained open after the last visit in the VAC-010 Study, those attributed to study vaccine in VAC-010 with onset after the participant exited VAC-010, those that were related to a VAC-011 procedure (i.e. blood draw, nasal swab sample), and all serious adverse events.
Measure: Number of Adverse Events (AE) Time: 32 weeks; for participants enrolled concurrently in Study VAC-010 adverse events were collected after the last VAC-010 visit through to Week 32.Description: Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 11A/D/E [11A] is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Prevalence of Streptococcus Pneumoniae Serotype 11A/D/E [11A] in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 13 is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Prevalence of Streptococcus Pneumoniae Serotype 13 in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 15A is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Prevalence of Streptococcus Pneumoniae Serotype 15A in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 15B/C [15B] is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Prevalence of Streptococcus Pneumoniae Serotype 15B/C [15B] in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 19A is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Prevalence of Streptococcus Pneumoniae Serotype 19A in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 19F is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Prevalence of Streptococcus Pneumoniae Serotype 19F in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 3 is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Prevalence of Streptococcus Pneumoniae Serotype 3 in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 35B is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Prevalence of Streptococcus Pneumoniae Serotype 35B in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 6A/B [6A] is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Prevalence of Streptococcus Pneumoniae Serotype 6A/B [6A] in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype NT4b is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Prevalence of Streptococcus Pneumoniae Serotype NT4b in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: The density of Streptococcus pneumoniae serotype 11A/D/E [11A] in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Density of Streptococcus Pneumoniae Serotype 11A/D/E [11A] in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: The density of Streptococcus pneumoniae serotype 13 in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Density of Streptococcus Pneumoniae Serotype 13 in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: The density of Streptococcus pneumoniae serotype 15A in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Density of Streptococcus Pneumoniae Serotype 15A in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: The density of Streptococcus pneumoniae serotype 15B/C [15B] in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Density of Streptococcus Pneumoniae Serotype 15B/C [15B] in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: The density of Streptococcus pneumoniae serotype 19A in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Density of Streptococcus Pneumoniae Serotype 19A in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: The density of Streptococcus pneumoniae serotype 19F in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Density of Streptococcus Pneumoniae Serotype 19F in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: The density of Streptococcus pneumoniae serotype 3 in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Density of Streptococcus Pneumoniae Serotype 3 in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: The density of Streptococcus pneumoniae serotype 35B in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Density of Streptococcus Pneumoniae Serotype 35B in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: The density of Streptococcus pneumoniae serotype 6A/B [6A] in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Density of Streptococcus Pneumoniae Serotype 6A/B [6A] in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32Description: The density of Streptococcus pneumoniae serotype NT4b in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
Measure: Density of Streptococcus Pneumoniae Serotype NT4b in the Nasopharynx Time: Week 0, Week 12, Week 16, Week 20, Week 32