Dose-Finding Study of S.Pneumoniae Whole Cell Vaccine Adsorbed to Alum (PATH-wSP) in Healthy Kenyan Adults and Toddlers

S. pneumoniae whole cell vaccine (SPWCV) is a vaccine candidate made from whole, unencapsulated pneumococcal cells. S. pneumoniae whole cell antigen bulk was manufactured at Walter Reed Army Institute of Research from strain RM200 RX1E PdT ΔlytA and is inactivated with beta-propiolactone. Pneumolysin, a proven virulence factor, was genetically knocked out in SPWCV and replaced with pneumolysoid, a derivative carrying the toxin gene with 3 point mutations known to abolish both cytolytic activity and complement activation. When adsorbed to aluminum hydroxide (alum), SPWCV is utilized as the vaccine candidate Streptococcus pneumoniae whole cell vaccine with aluminum hydroxide adjuvant (PATH-wSP) for clinical investigation. PATH-wSP has been previously tested in adults in a Phase 1 trial in the US, in which doses of 100 to 600 μg were given to healthy young adults in a 3-vaccination series and showed a favorable safety, tolerability, and immunogenicity profile.

This study was a dose escalation and age de-escalation study, and sequential cohorts of subjects were identified to allow safety evaluations of dosing and ages to occur progressively during the study. The following PATH-wSP cohorts were defined for adult and toddler subjects:

* Adult Cohort 1: 600 μg PATH-wSP or saline
* Adult Cohort 2: 1000 μg PATH-wSP or saline
* Toddler Cohort 1: 300 μg PATH-wSP and/or active control vaccines
* Toddler Cohort 2: 600 μg PATH-wSP and/or active control vaccines.

• PATH-wSP (Biological): Streptococcus pneumoniae Whole Cell Vaccine adsorbed to Alum
• Synflorix (Biological), also known as 10-valent Pneumococcal Conjugate Vaccine (PCV10): 1 dose (0.5 mL) contains: 1 μg of each of the following pneumococcal polysaccharide serotypes: 1, 5, 6B, 7F, 9V, 14, and 23 F And 3 μg of the following pneumococcal polysaccharide serotypes: 4, 18C and 19F. The serotypes are conjugated to either: protein D (derived from Non-Typeable Haemophilus influenzae) carrier protein, tetanus toxoid carrier protein or diphtheria toxoid carrier protein
• Pentavac (Biological), also known as Diptheria Pertussis Tetanus Hep B Haemophilus b Conjugate: Each PFS contains 0.5 ml (single dose): Diphtheria Toxoid 20 Lf to 30 Lf Tetanus Toxoid 2.5 Lf to 10 Lf B. Pertussis 4 IU HBsAg (rDNA) 10 mcg Purified capsular HIB Polysaccharide (PRP) Conjugated to Tetanus Toxoid (carrier protein) 10 mcg Adsorbed on Aluminium Phosphate, AL+++ 1.25 mg Preservative: Thiomersal 0.005 % Dose: O.5ml by intramuscular injection.
• Saline (Other): 0.9% Sodium Chloride Injection, USP

Primary outcomes

• Number/Percent of Adult Subjects Experiencing Fatigue/Malaise Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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.
• Number/Percent of Adult Subjects Experiencing Myalgia Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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.
• Number/Percent of Adult Subjects Experiencing Headache Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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.
• Number/Percent of Adult Subjects Experiencing Pain at Injection Site Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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.
• Number/Percent of Adult Subjects Experiencing Tenderness at Injection Site Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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.
• Number/Percent of Adult Subjects Experiencing Induration at Injection Site Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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
• Number/Percent of Adult Subjects Experiencing Fever at Injection Site Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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.
• Number/Percent of Toddler Subjects Experiencing Fever Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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.
• Number/Percent of Toddler Subjects Experiencing Cutaneous Rash Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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
• Number/Percent of Toddler Subjects Experiencing Irritability Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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).
• Number/Percent of Toddler Subjects Experiencing Drowsiness Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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).
• Number/Percent of Toddler Subjects Experiencing Loss of Appetite Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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).
• Number/Percent of Toddler Subjects Experiencing Pain/Tenderness at Injection Site Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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.
• Number/Percent of Toddler Subjects Experiencing Induration/Swelling at Injection Site Following Vaccination [up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)]: 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).

Secondary outcomes

• Geometric Mean Concentrations (GMC) of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: ELISA Assay [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured with enzyme-linked immunosorbent assay (ELISA).
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: ELISA Assay [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured with enzyme-linked immunosorbent assay (ELISA).
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against L460D Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using meso scale discovery (MSD).
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: Meso Scale Discovery (MSD) Assay [0 days, 28 days (Dose 1) and 56 days (Dose 2)]
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against PhtD Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using Meso Scale Discovery (MSD) Assay
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against BCH0785 Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using Meso Scale Discovery (MSD) Assay
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against StkP Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using Meso Scale Discovery (MSD) Assay
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against PcpA Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using Meso Scale Discovery (MSD) Assay
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against SPWCA Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: MSD Assay
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against PiuA Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: MSD Assay
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against PiaA Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: MSD Assay
• Geometric Mean Fold Change of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: ELISA [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using ELISA
• Geometric Mean Fold Change of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: ELISA [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using ELISA
• Geometric Mean Fold Change of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: MSD [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using MSD
• Geometric Mean Fold Change of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: MSD [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using ELISA
• Geometric Mean Fold Change of IgG Antibodies Against PhtD Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using MSD
• Geometric Mean Fold Change of IgG Antibodies Against BCH0785 Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using MSD
• Geometric Mean Fold Change of IgG Antibodies Against StkP Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using MSD
• Geometric Mean Fold Change of IgG Antibodies Against PcpA Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using MSD
• Geometric Mean Fold Change of IgG Antibodies Against SPWCA Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using MSD
• Geometric Mean Fold Change of IgG Antibodies Against PiuA Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using MSD
• Geometric Mean Fold Change of IgG Antibodies Against PiaA Pneumococcal Protein [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: Measured using MSD
• Fold Change in IgG Response to Pneumolysoid (L460D) Pneumococcal Protein Among Toddler Cohort (ELISA) [28 days (post-vaccination 1) and 56 days (post-vaccination 2)]: Measured using ELISA
• Fold Change in IgG Response to PspA-Fam1 (ELISA) [28 days (post-vaccination 1) and 56 days (post-vaccination 2)]: Measured using ELISA
• Fold Change in IgG Response to L460D Pneumococcal Protein (MSD) [28 days (post-vaccination 1) and 56 days (post-vaccination 2)]: Measured using MSD
• Fold Change in IgG Response to PspA-Fam1 Pneumococcal Protein (MSD) [28 days (post-vaccination 1) and 56 days (post-vaccination 2)]: Measured using MSD
• Fold Change in IgG Response to PhtD Pneumococcal Protein [28 days (post-vaccination 1) and 56 days (post-vaccination 2)]: Measured using MSD
• Fold Change in IgG Response to BCH0785 Pneumococcal Protein [28 days (post-vaccination 1) and 56 days (post-vaccination 2)]: Measured using MSD
• Fold Change in IgG Response to StkP Pneumococcal Protein [28 days (post-vaccination 1) and 56 days (post-vaccination 2)]: Measured using MSD
• Fold Change in IgG Response to PcpA Pneumococcal Protein [28 days (post-vaccination 1) and 56 days (post-vaccination 2)]: Measured using MSD
• Fold Change in IgG Response to SPWCA Pneumococcal Protein [28 days (post-vaccination 1) and 56 days (post-vaccination 2)]: Measured using MSD
• Fold Change in IgG Response to PiuA Pneumococcal Protein [28 days (post-vaccination 1) and 56 days (post-vaccination 2)]: Measured using MSD
• Fold Change in IgG Response to PiaA Pneumococcal Protein [28 days (post-vaccination 1) and 56 days (post-vaccination 2)]: Measured using MSD
• Number/Percentage of Adult Subjects With Neutralizing Antibody Response to Pneumolysin [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: 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).
• Number/Percentage of Toddler Subjects With Neutralizing Antibody Response to Pneumolysin [0 days, 28 days (Dose 1) and 56 days (Dose 2)]: 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).

Other outcomes

• Geometric Mean Concentration (GMCs) of PNC-IgG Serotypes Among Toddler Subjects [12 weeks (Cohort 1) and 4 weeks (Cohort 2) post-vaccination 1]: 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.
• Geometric Mean Concentration (GMC) Ratio of Diptheria Booster Immune Response Among Toddler Subjects [12 weeks post vaccination 1]: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.
• Geometric Mean Concentration (GMC) Ratio of Hepatitis B Booster Immune Response Among Toddler Subjects [12 weeks post vaccination 1]: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.
• Geometric Mean Concentration (GMC) Ratio of Haemophilus Influenzae Type b (Hib) Booster Immune Response Among Toddler Subjects [12 weeks post vaccination 1]: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.
• Geometric Mean Concentration (GMC) Ratio of Pertussis FHA and Pertussis Toxin Immune Response Among Toddler Subjects [12 weeks post vaccination 1]: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.
• Geometric Mean Concentration (GMC) Ratio of Pertussis Fimbriae Immune Response Among Toddler Subjects [12 weeks post vaccination 1]: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.
• Geometric Mean Concentration (GMC) Ratio of Tetanus Booster Immune Response Among Toddler Subjects [12 weeks post vaccination 1]: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.

Sex: All, ages: 12 Months to 45 Years, accepts healthy volunteers

Inclusion Criteria:

* Healthy young Kenyan adults between 18 to 45 years of age
* Willing to provide written informed consent, able to understand comply with study requirements/procedures.
* Adult female subjects surgically sterilized or with a negative serum pregnancy test on enrollment and prior to each vaccination. Adult females must be willing to avoid becoming pregnant over the duration of the study, and must agree to employ an effective form of birth control for the duration of the study.
* Subjects willing to avoid consumption of herbal medication (including herbal medication taken by a mother, which may transmit to a toddler through breast milk) that could have effects on liver function or bleeding indices during the course of the study.
* Healthy toddlers between 12 to 15 months of age who have completed their primary EPI vaccines.
* Toddler's parent willing to provide written informed consent for subject, able to understand and comply with study requirements and procedures.
* Not premature, had a birth weight of >2.5 kg, and a weight-to-height Z score of ≥ -2 at the time of enrollment.

Exclusion Criteria:

* Use of any investigational or nonregistered drug within 90 days prior and during the course of study participation.
* History of administration of any vaccine within 30 days prior to administration of study vaccine or planned vaccination during the course of study.
* History of anaphylactic shock.
* Positive test for malaria (blood film) at time of screening and when retested at Visit 1.
* Immunosuppression or immunodeficiency, inclusive of human immunodeficiency virus, by medical history or by testing at screening.
* Chronic, clinically significant pulmonary, cardiovascular, hepatobiliary, gastrointestinal, renal, neurological, or hematological functional abnormality or major congenital defects or illness that requires medical therapy, as deemed by medical history or clinical assessment.
* Evidence of active hepatitis infection (B or C) by immunologic testing at screening.
* Any medical or social condition that in the opinion of the investigator will interfere with the study objectives or pose a risk to the study subject or may prevent the subject from completing the study follow-up.
* An employee (or first degree relative of employee) of the Sponsor, the Clinical Research Organization, or any investigator or site personnel.
* Any screening laboratory test result or vital sign measurement outside normal parameters and deemed by the clinician to be clinically significant, including a positive test for malaria.
* Acute illness (moderate or severe) and/or fever (tympanic temperature >38°C for adults and >37.5°C for toddlers), or any acute and limited illness requiring medical treatment, including the use of antibiotics and treatment for parasites.
* History of allergic disease or history of a serious reaction to any prior vaccination or known hypersensitivity to any component of the study vaccines.
* Disorders that require chronic administration of immune-modifying drugs within the past 6 months prior to the administration of the study vaccine.
* Administration of immunoglobulins and/or any blood products within the 6 months preceding enrollment in the study; or anticipation of such administration during the study period.
* Known disturbance of coagulation or other blood disorder in adult subject or in self/first degree relative of toddler subject; or receipt of anticoagulants in the past 3 weeks.
* History of meningitis or seizures or any neurological disorder or major psychiatric disorder (adult).
* Female subjects who are pregnant or breast-feeding.
* Suspicion or recent history of alcohol or substance abuse.
* Toddlers with evidence of congenital abnormality or developmental delay.
* Toddlers with evidence of fetal alcohol syndrome or history of alcohol abuse in mother during pregnancy.
* Toddlers exposed to HIV, born of an HIV infected mother, or who are HIV positive by either antibody or polymerase chain reaction testing.

Participant flow

Outcome results

• Number/Percent of Adult Subjects Experiencing Fatigue/Malaise Following Vaccination (Primary), Count of participants, Participants: PATH-wSP (600 mcg): Vaccination 1 15; PATH-wSP (1000 mcg): Vaccination 1 15; Saline: Vaccination 1 18; PATH-wSP (600 mcg): Vaccination 2 16; PATH-wSP (1000 mcg): Vaccination 2 13; Saline: Vaccination 2 15
• Number/Percent of Adult Subjects Experiencing Myalgia Following Vaccination (Primary), Count of participants, Participants: PATH-wSP (600 mcg): Vaccination 1 11; PATH-wSP (1000 mcg): Vaccination 1 16; Saline: Vaccination 1 17; PATH-wSP (600 mcg): Vaccination 2 15; PATH-wSP (1000 mcg): Vaccination 2 16; Saline: Vaccination 2 15
• Number/Percent of Adult Subjects Experiencing Headache Following Vaccination (Primary), Count of participants, Participants: PATH-wSP (600 mcg): Vaccination 1 16; PATH-wSP (1000 mcg): Vaccination 1 12; Saline: Vaccination 1 13; PATH-wSP (600 mcg): Vaccination 2 15; PATH-wSP (1000 mcg): Vaccination 2 11; Saline: Vaccination 2 12
• Number/Percent of Adult Subjects Experiencing Pain at Injection Site Following Vaccination (Primary), Count of participants, Participants: PATH-wSP (600 mcg): Vaccination 1 4; PATH-wSP (1000 mcg): Vaccination 1 3; Saline: Vaccination 1 14; PATH-wSP (600 mcg): Vaccination 2 9; PATH-wSP (1000 mcg): Vaccination 2 5; Saline: Vaccination 2 16
• Number/Percent of Adult Subjects Experiencing Tenderness at Injection Site Following Vaccination (Primary), Count of participants, Participants: PATH-wSP (600 mcg): Vaccination 1 3; PATH-wSP (1000 mcg): Vaccination 1 4; Saline: Vaccination 1 11; PATH-wSP (600 mcg): Vaccination 2 7; PATH-wSP (1000 mcg): Vaccination 2 7; Saline: Vaccination 2 16
• Number/Percent of Adult Subjects Experiencing Induration at Injection Site Following Vaccination (Primary), Count of participants, Participants: PATH-wSP (600 mcg): Vaccination 1 13; PATH-wSP (1000 mcg): Vaccination 1 17; Saline: Vaccination 1 17; PATH-wSP (600 mcg): Vaccination 2 18; PATH-wSP (1000 mcg): Vaccination 2 16; Saline: Vaccination 2 18
• Number/Percent of Adult Subjects Experiencing Fever at Injection Site Following Vaccination (Primary), Count of participants, Participants: PATH-wSP (600 mcg): Vaccination 1 18; PATH-wSP (1000 mcg): Vaccination 1 18; Saline: Vaccination 1 18; PATH-wSP (600 mcg): Vaccination 2 18; PATH-wSP (1000 mcg): Vaccination 2 17; Saline: Vaccination 2 18
• Number/Percent of Toddler Subjects Experiencing Fever Following Vaccination (Primary), Count of participants, Participants: PATH-wSP (300 mcg)+Active Control: Vaccination 1 26; PATH-wSP (300 mcg)+Saline: Vaccination 1 40; PATH-wSP (600 mcg)+Active Control: Vaccination 1 31; PATH-wSP (600 mcg)+Saline: Vaccination 1 42; Active Control Only: Vaccination 1 37; PATH-wSP (300 mcg): Vaccination 2 87; PATH-wSP (600 mcg): Vaccination 2 78; Saline: Vaccination 2 42
• Number/Percent of Toddler Subjects Experiencing Cutaneous Rash Following Vaccination (Primary), Count of participants, Participants: PATH-wSP (300 mcg)+Active Control: Vaccination 1 41; PATH-wSP (300 mcg)+Saline: Vaccination 1 44; PATH-wSP (600 mcg)+Active Control: Vaccination 1 43; PATH-wSP (600 mcg)+Saline: Vaccination 1 39; Active Control Only: Vaccination 1 40; PATH-wSP (300 mcg): Vaccination 2 83; PATH-wSP (600 mcg): Vaccination 2 72; Saline: Vaccination 2 38
• Number/Percent of Toddler Subjects Experiencing Irritability Following Vaccination (Primary), Count of participants, Participants: PATH-wSP (300 mcg)+Active Control: Vaccination 1 31; PATH-wSP (300 mcg)+Saline: Vaccination 1 46; PATH-wSP (600 mcg)+Active Control: Vaccination 1 36; PATH-wSP (600 mcg)+Saline: Vaccination 1 49; Active Control Only: Vaccination 1 40; PATH-wSP (300 mcg): Vaccination 2 90; PATH-wSP (600 mcg): Vaccination 2 89; Saline: Vaccination 2 47
• Number/Percent of Toddler Subjects Experiencing Drowsiness Following Vaccination (Primary), Count of participants, Participants: PATH-wSP (300 mcg)+Active Control: Vaccination 1 48; PATH-wSP (300 mcg)+Saline: Vaccination 1 49; PATH-wSP (600 mcg)+Active Control: Vaccination 1 47; PATH-wSP (600 mcg)+Saline: Vaccination 1 50; Active Control Only: Vaccination 1 50; PATH-wSP (300 mcg): Vaccination 2 95; PATH-wSP (600 mcg): Vaccination 2 94; Saline: Vaccination 2 47
• Number/Percent of Toddler Subjects Experiencing Loss of Appetite Following Vaccination (Primary), Count of participants, Participants: PATH-wSP (300 mcg)+Active Control: Vaccination 1 32; PATH-wSP (300 mcg)+Saline: Vaccination 1 42; PATH-wSP (600 mcg)+Active Control: Vaccination 1 30; PATH-wSP (600 mcg)+Saline: Vaccination 1 47; Active Control Only: Vaccination 1 31; PATH-wSP (300 mcg): Vaccination 2 85; PATH-wSP (600 mcg): Vaccination 2 88; Saline: Vaccination 2 45
• Number/Percent of Toddler Subjects Experiencing Pain/Tenderness at Injection Site Following Vaccination (Primary), Count of participants, Participants: 300 mcg PATH-wSP: Vaccination 1 33; 600 mcg PATH-wSP: Vaccination 1 43; Active Control: Pentavac 17; Active Control: Synflorix 21; Active Control: Saline 20; PATH-wSP (300 mcg): Vaccination 2 72; PATH-wSP (600 mcg): Vaccination 2 81; Saline: Vaccination 2 42
• Number/Percent of Toddler Subjects Experiencing Induration/Swelling at Injection Site Following Vaccination (Primary), Count of participants, Participants: 300 mcg PATH-wSP: Vaccination 1 93; 600 mcg PATH-wSP: Vaccination 1 98; Active Control: Pentavac 45; Active Control: Synflorix 48; Active Control: Saline 49; PATH-wSP (300 mcg): Vaccination 2 93; PATH-wSP (600 mcg): Vaccination 2 89; Saline: Vaccination 2 47
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: ELISA Assay (Secondary), Geometric mean, titer: Adult Cohort: PATH-wSP (600 mcg) 2083.27 (1638.67 to 2648.49); Adult Cohort: PATH-wSP (1000 mcg) 1569.91 (1102.09 to 2236.30); Adult Cohort: Saline 1998.33 (1356.41 to 2944.02); Toddler Cohort: PATH-wSP (300 mcg)+Active Control 400.00 (289.99 to 551.74); Toddler Cohort: PATH-wSP (300 mcg)+Saline 311.30 (209.43 to 462.71); Toddler Cohort: PATH-wSP (600 mcg)+Active Control 755.10 (541.85 to 1052.27); Toddler Cohort: PATH-wSP (600 mcg)+Saline 848.61 (612.56 to 1175.62); Toddler Cohort: Active Control Only 455.52 (318.02 to 652.45)
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: ELISA Assay (Secondary), Geometric mean, titer: Adult Cohort: PATH-wSP (600 mcg) 1899.32 (1393.87 to 2588.06); Adult Cohort: PATH-wSP (1000 mcg) 2042.68 (1679.25 to 2484.75); Adult Cohort: Saline 1793.44 (1404.90 to 2289.43); Toddler Cohort: PATH-wSP (300 mcg)+Active Control 410.23 (298.75 to 563.30); Toddler Cohort: PATH-wSP (300 mcg)+Saline 361.41 (268.84 to 485.85); Toddler Cohort: PATH-wSP (600 mcg)+Active Control 550.02 (423.69 to 714.03); Toddler Cohort: PATH-wSP (600 mcg)+Saline 674.04 (509.70 to 891.36); Toddler Cohort: Active Control Only 456.64 (349.76 to 596.17)
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against L460D Pneumococcal Protein (Secondary), Geometric mean, titer: Adult Cohort: PATH-wSP (600 mcg) 861.27 (661.13 to 1121.99); Adult Cohort: PATH-wSP (1000 mcg) 820.92 (629.25 to 1070.97); Adult Cohort: Saline 908.51 (582.64 to 1416.63); Toddler Cohort: PATH-wSP (300 mcg)+Active Control 263.85 (206.73 to 336.74); Toddler Cohort: PATH-wSP (300 mcg)+Saline 210.15 (160.30 to 275.48); Toddler Cohort: PATH-wSP (600 mcg)+Active Control 309.74 (246.74 to 388.83); Toddler Cohort: PATH-wSP (600 mcg)+Saline 331.08 (270.14 to 405.77); Toddler Cohort: Active Control Only 216.45 (173.79 to 269.58)
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: Meso Scale Discovery (MSD) Assay (Secondary), Geometric mean, titer: Adult Cohort: PATH-wSP (600 mcg) 2124.32 (1533.58 to 2942.62); Adult Cohort: PATH-wSP (1000 mcg) 2129.61 (1574.00 to 2881.35); Adult Cohort: Saline 2049.33 (1457.58 to 2881.30); Toddler Cohort: PATH-wSP (300 mcg)+Active Control 175.80 (122.62 to 252.03); Toddler Cohort: PATH-wSP (300 mcg)+Saline 174.35 (119.81 to 253.71); Toddler Cohort: PATH-wSP (600 mcg)+Active Control 202.89 (145.92 to 282.09); Toddler Cohort: PATH-wSP (600 mcg)+Saline 217.24 (154.08 to 306.29); Toddler Cohort: Active Control Only 177.29 (127.64 to 246.25)
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against PhtD Pneumococcal Protein (Secondary), Geometric mean, titer: Adult Cohort: PATH-wSP (600 mcg) 841.63 (626.89 to 1129.94); Adult Cohort: PATH-wSP (1000 mcg) 784.56 (606.58 to 1014.75); Adult Cohort: Saline 775.26 (531.41 to 1130.99); Toddler Cohort: PATH-wSP (300 mcg)+Active Control 426.11 (313.40 to 579.35); Toddler Cohort: PATH-wSP (300 mcg)+Saline 403.13 (289.64 to 561.09); Toddler Cohort: PATH-wSP (600 mcg)+Active Control 466.20 (337.37 to 644.21); Toddler Cohort: PATH-wSP (600 mcg)+Saline 497.28 (383.30 to 645.15); Toddler Cohort: Active Control Only 434.86 (331.26 to 570.85)
• Geometric Mean Concentrations (GMC) of IgG Antibodies Against BCH0785 Pneumococcal Protein (Secondary), Geometric mean, titer: Adult Cohort: PATH-wSP (600 mcg) 1566.50 (1035.43 to 2369.96); Adult Cohort: PATH-wSP (1000 mcg) 1145.05 (909.05 to 1442.33); Adult Cohort: Saline 1236.11 (819.09 to 1865.46); Toddler Cohort: PATH-wSP (300 mcg)+Active Control 400.58 (294.10 to 545.61); Toddler Cohort: PATH-wSP (300 mcg)+Saline 271.66 (200.93 to 367.30); Toddler Cohort: PATH-wSP (600 mcg)+Active Control 281.66 (209.24 to 379.16); Toddler Cohort: PATH-wSP (600 mcg)+Saline 372.53 (277.67 to 499.79); Toddler Cohort: Active Control Only 288.13 (206.26 to 402.50)
• 36 more outcome measures not shown.

Adverse events

Time frame: 4 weeks post-vaccination

Serious adverse events by term

Other adverse events by term

25 more terms not shown.

• Nekoye Otsyula, MD, Principal investigator, Kenya Medical Research Institute/Walter Reed Project