Enrolment, randomization, vaccination and follow-up

Children who met the eligibility criteria were randomized at 1 month of age to receive 10vPCV or 13vPCV using a computer-generated random number list. This assignment was specified inside a sealed envelope with the next sequential number and kept in the participant’s personal folder. Throughout the study laboratory staff was blinded to the group allocation. The vaccine and specimen collection schedules are shown in Table 1. Prior to any vaccination (and PPV challenge at age 23 months), study nurses/HEOs obtained a medical history and examined children to exclude contraindications for vaccination (including temperature ≥ 38 °C, anaphylaxis to previous vaccination, serious neurological illness within 48 h of previous pentavalent vaccine) and specimens were collected. Routine childhood vaccines (including pentavalent whole-cell pertussis, diphtheria, tetanus, Hepatitis B and Haemophilus influenzae type B (Hib) vaccine and oral polio vaccine; see Table ​Table1)1) were administered by the study HEOs/nurses at 1, 2, and 3 months of age, together with the 10vPCV or 13vPCV study vaccines. Information on birth doses of Bacillus Calmette-Guérin (BCG) vaccine and Hepatitis B vaccines administered by hospital staff was collected from hospital records, as were birth weights. At the initial visit mothers were given a follow-up card on which dates for future visits were recorded. Children living in rural areas were generally transported to and from the clinic while urban residents were either brought in or came of their own accord to the clinic following a reminder by mobile phone. At age 4 months children attended the clinic for specimen collection only. At age 6 months, children received their first dose of measles vaccine and a dose of Vitamin A either at the PNGIMR clinic or at other child health clinics. At age 9 months children received a second dose of measles vaccine and Vitamin A, and were randomized within each PCV group to receive or not receive PPV. The PPV group allocation was assigned at enrolment, at the same time as PCV randomization, but kept in an unopened envelope until the 9-month visit. Specimens were collected before vaccination and again 4 weeks later.

Vaccination and specimen collection schedule

BCG Bacillus Calmette-Guérin vaccine; HepB Hepatitis B vaccine; Pentavalent is a diphtheria, tetanus, whole cell pertussis, Haemophilus influenzae type B, Hepatitis B combination vaccine; PCV 10-valent or 13-valent pneumococcal conjugate vaccine; OPV oral polio vaccine; PPV 23-valent pneumococcal polysaccharide vaccine; NPS nasopharyngeal swab; PBMC peripheral blood mononuclear cells

^aBirth doses of BCG and Hepatitis B were given by hospital nurses before enrolment of infants into the study

^bPCV and PPV are study vaccines while the other vaccines were routine EPI vaccines in PNG at the time of the trial

^cMorbidity surveillance was conducted throughout the duration of the trial. Vitamin A was given at 6 and 9 months of age

All participants were given a 1/5^th challenge dose of PPV at age 23 months with specimens collected immediately before the challenge and 4 weeks later. All vaccinations were documented in the child’s health book held by the mother/guardian and also written on the child’s follow-up card, which was stored electronically. Photocopies of records in the parent-held books (which include information on any illness episode) were stored in the child’s personal folder.

Every effort was made to locate participants for follow-up in a timely manner. Between 10 and 23 months, nurses and field staff attempted to contact participants’ caregivers at least twice to find out about any intervening illness and changes in address. Children were withdrawn from the study if the child could not be located on 3 home visits or information had been obtained from relatives that the family had moved out of the study area permanently, or if parents withdrew their consent for continuation in the study. Children were also withdrawn by the investigators following a protocol violation.