Comparison of two schedules of two-dose priming with the ten-valent pneumococcal conjugate vaccine in Nepalese children: an open-label, randomised non-inferiority controlled trial

Abstract

Background: Nepalese infants receive PCV10 with a one-month interval between priming doses for programmatic reasons. We aimed to investigate whether immune responses to PCV10 serotypes were non-inferior if the second priming dose of PCV10 was delivered at a one-month as opposed to a two-month interval. Methods: We conducted an open-label, randomised, parallel group trial in healthy Nepalese infants aged 40-60 days in Kathmandu, Nepal. Participants were randomised (1:1) using a computer-generated list with randomly varying permuted block sizes accessed through a validated web-based interface, to receive PCV10 at 6 and 10 weeks (6+10) or 6 and 14 weeks (6+14) of age, with both groups receiving a booster at 9 months of age. Laboratory staff, blinded to study intervention, analysed sera for antibodies against PCV10 serotypes by ELISA. The primary objective, using the intention-to-treat population, was to determine whether the 6+10 schedule was non-inferior to the 6+14 schedule at 9 months of age, based on the proportion of infants with serotype-specific IgG ≥ 0•35 μg/mL and a 10% margin. Secondary objectives included, determining if there were any differences between the groups when comparing the proportion of infants with serotype-specific IgG ≥ 0•35 μg/mL. This trial is registered at ClinicalTrials.gov, number NCT02385513.

Immunogenicity of alternative ten-valent pneumococcal conjugate vaccine schedules in infants in Ho Chi Minh City, Vietnam: results from a single-blind, parallel-group, open-label, randomised, controlled trial

“… 11 , 12 Another trial from Nepal found that a 2-month interval between doses in a primary series resulted in a higher antibody response than a 1-month interval. 13 Therefore, timing of doses during the primary vaccination series is an important consideration because maximising protection against invasive pneumococcal disease in the intervening period until the booster dose is crucial.…”

Persistence of Immunity Following 2-Dose Priming with a 10-Valent Pneumococcal Conjugate Vaccine at 6 and 10 Weeks or 6 and 14 Weeks of Age in Nepalese Toddlers

“…We conducted a cross-sectional follow-up study at Patan Hospital among participants of our previous trial comparing different 2-dose priming schedules (6 + 10 weeks vs. 6 + 14 weeks) for PCV10. 14 Oxford Tropical Research Ethics Committee (OxTREC Ref no: 34-17) and Nepal Health Research Council (NHRC Reg no: 459/2017) approved this study.…”

“…We conducted a cross-sectional follow-up study at Patan Hospital among participants of our previous trial comparing different 2-dose priming schedules (6 + 10 weeks vs. 6 + 14 weeks) for PCV10. 14 We approached by telephone, 287 participants who completed the original study, and explained the details of the study to them. We invited interested participants to visit the Paediatric Research Unit at Patan Hospital, where we provided them with an information sheet and discussed the study in more detail.…”

“…13 In 2015, PCV10 vaccine was introduced into the routine immunization schedule in Nepal, supported by the evidence we had generated, but with a unique 2 + 1 dosing schedule using 6-week and 10-week priming schedule with a booster at 9 months of age. 14 The scheduling was selected to avoid multiple injections at 14 weeks in the national immunization schedule, as implementation happened around the time that a single dose of an inactivated poliomyelitis virus vaccine was introduced at 14 weeks of age. The use of more than 2 injections at an immunization visit was believed to be a concern for parents and vaccinators.…”

“…The study demonstrated that the schedule with 2 priming doses at 6 and 10 weeks of age and a 9-month booster were inferior to the schedule with 2 priming doses at 6 and 14 weeks of age and a 9-month booster for immunogenicity against some serotypes at 9 months (before boosting), but there were no significant differences at 10 months of age (1-month post-boosting). 14 To our knowledge, there are no prior studies that have directly compared the persistence of immunity, beyond the second year of life, in these 2 PCV schedules with different prime dose timings. We, therefore, undertook this study to examine the persistence of immunity in healthy Nepalese infants at 2–3 years of age, following PCV10 immunization at 6 and 10 weeks or 6 and 14 weeks of age, both with a booster at 9 months of age.…”