Nasopharyngeal Carriage Study in Healthy Kenyan Toddlers

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.

This study enrolled healthy Kenyan toddlers (12-15 months of age) who participated in the randomized control trial of VAC-010 (NCT02097472), as well as healthy toddlers aged 12 to 15 months who had not participated in the VAC-010 Study. All participants must have received a primary dose of pneumococcal conjugate vaccine (PCV) per local practice prior to enrollment in either VAC-010 or VAC-011. No treatments were administered during this study.

The study consisted of the following four groups:

Participants who were randomized in study VAC-010 (2:2:1 ratio), defined according to the treatment received in VAC-010:

* 1. PATH-wSP + Booster
* 2. PATH-wSP Only
* 3. Booster Only

Participants who did not participate in VAC-010:

* 4. No Intervention

Each group consisted of 2 cohorts of participants, Cohort 1 (300 µg PATH-wSP) and Cohort 2 (600 µg PATH-wSP). Enrollment into Cohorts 1 and 2 occurred sequentially; participants in groups 3 and 4 who did not receive PATH-wSP were also enrolled over time and allocated into one of the two cohorts (300 and 600 µg) in order to control for potential seasonal variation in the NPC of S. pneumoniae.

Each participant completed a total of 5 scheduled visits. For toddlers enrolled simultaneously in VAC-010, visits corresponded to enrollment (Baseline) and 4, 8, 12, and 24 weeks post final vaccination in VAC-010. For toddlers in the No Intervention group, the first visit corresponded to Baseline and the second to fifth visits corresponded to 12, 16, 20, and 32 weeks later. Nasopharyngeal swabs were taken at each visit following World Health Organization (WHO) guidelines for analysis of nasopharyngeal burden.

Treatments received during VAC-010 included:

* PATH-wSP: Streptococcus pneumoniae whole cell vaccine with aluminum hydroxide adjuvant
* Synflorix™ booster vaccine: pneumococcal polysaccharide conjugate vaccine (adsorbed)
* Pentavac booster vaccine: diphtheria, tetanus, pertussis (Whole Cell), hepatitis B (recombinant deoxyribonucleic acid \[rDNA\]) and Haemophilus influenzae type b conjugate vaccine (adsorbed).
* Saline control

Eligibility Criteria:
Inclusion Criteria:

- For Toddlers Enrolled in VAC-010 (NCT02097472):

* Randomization in VAC-010.
* Subject's parent must provide voluntary written informed consent for subject to participate in the study, is fully capable of comprehending and complying with study requirements and procedures, able and willing to return for all scheduled follow-up visits, and has expressed availability for the required study period, with access to a consistent means of telephone contact. An illiterate parent will require an impartial witness to be present during consenting process to include discussing the consent form, verbal consent and thumb-printing.
* Subject has not completed his or her final vaccination in VAC-010.

For Toddlers NOT Enrolled in VAC-010 (PCV-primed-only cohort):

* Healthy Kenyan toddlers between 12 to 15 (inclusive) months of age who have completed their primary Expanded Programme on Immunization (EPI) vaccines, with the exception that the birth dose of oral polio vaccine is not required.
* Subjects who have not received a PCV booster following primary PCV series.
* Subject's parent must provide voluntary written informed consent for subject to participate in the study, is fully capable of comprehending and complying with study requirements and procedures, able and willing to return for all scheduled follow-up visits, and has expressed availability for the required study period, with access to a consistent means of telephone contact. An illiterate parent will require an impartial witness to be present during consenting process to include discussing the consent form, verbal consent and thumb-printing.
* Subjects who were not born premature, had a birth weight of \> 2.5 kg, and who have a weight-to-height Z-score of ≥ -2 at the time of enrollment.

Exclusion Criteria:

- For Toddlers NOT enrolled in VAC-010 (PCV-primed only):

* Use of any investigational or non-registered drug within 90 days prior to screening, or planned during the course of study participation.
* Immunosuppression or immunodeficiency (inclusive of human immunodeficiency virus \[HIV\]) by medical history (inclusive of possible HIV through maternal fetal transfer at time of birth or through breast milk).
* Chronic, clinically significant pulmonary, cardiovascular, hepatobiliary, gastrointestinal, renal, neurological, or hematological functional abnormality or major congenital defects or illness that requires medical therapy, by medical history or clinical assessment. This includes abnormal vital signs as assessed by toxicity scoring.
* Any medical or social condition that in the opinion of the investigator may interfere with the study objectives, pose a risk to the study subject, or prevent the subject from completing the study.
* An employee (or first degree relative of employee) of the Sponsor, the Clinical Research Organization (CRO), the investigator or any site personnel.
* Disorders that required chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within the 6 months prior to enrollment. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose \>10 mg of prednisone (adult dosage) adjusted for equivalent dosing in toddlers by weight. The use of topical glucocorticoids will be permitted.
* 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.
* History of meningitis, seizures or any neurological disorder.
* Subject who has evidence of congenital abnormality or developmental delay.
* Any evidence of fetal alcohol syndrome or history of alcohol abuse in mother during pregnancy.