by Rama Kandasamy, DPhil; Meeru Gurung, MD; Stephen Thorson, MD; Ly-Mee Yu, DPhil; Ushma Galal, MSc; Merryn Voysey, MBiostat; Sarah Kelly, MSc; Brian Wahl, PhD; Guy Berbers, PhD; Kier Finnegan, MSc; Imran Ansari, MD; Krishna Paudel, MD; Prof David R Murdoch, MD; Katherine L O'Brien, MD; Dominic F Kelly, PhD; Prof David Goldblatt, PhD; Prof Shrijana Shrestha, MD; and Prof Andrew J Pollard, FMedSci.
Published in The Lancet Infectious Diseases, 08 January 2019. DOI: https://doi.org/10.1016/S1473-3099(18)30568-1
Nepalese infants receive ten-valent pneumococcal conjugate vaccine (PCV10) with a 1 month interval between priming doses for programmatic reasons. Researchers aimed to investigate whether immune responses to PCV10 serotypes were non-inferior if the second priming dose of PCV10 was delivered at a 1 month interval as opposed to a 2 month interval. Researchers conducted an open-label, randomised, parallel group trial in healthy Nepalese infants aged 40–60 days at Patan Hospital, Kathmandu, Nepal. Children were eligible for inclusion if they were healthy, were born at more than or equal to 37 weeks' gestation, were residing in Kathmandu, and had not had any previous vaccinations other than BCG, and oral polio vaccine. Participants were randomly assigned (1:1) by means of a computer-generated list with randomly varying permuted block sizes accessed through a validated web-based interface, to receive PCV10 either at 6 weeks and 10 weeks of age (6 + 10 group) or at 6 weeks and 14 weeks of age (6 + 14 group), with both groups receiving a booster at 9 months of age. Laboratory staff, masked to study intervention, analysed serum samples for antibodies against PCV10 serotypes by ELISA. The primary outcome was to determine whether the 6 + 10 schedule was non-inferior to the 6 + 14 schedule at 9 months of age, on the basis of the proportion of infants with serotype-specific IgG greater than or equal to 0·35 μg/mL. Non-inferiority was established with a 10% margin, and the primary endpoint was measured in a modified intention-to-treat population, which included only participants who successfully had a blood sample collected. Researchers concluded that the 6 week, 14 week, and 9 month schedule should be implemented where possible. However, post-booster responses, which are thought to drive herd immunity, were similar in the two schedules. Therefore, the 6 week, 10 week, and 9 month schedule is an alternative that can be used when logistically necessary, and is expected to provide herd protection. This trial is registered at ClinicalTrials.gov, number NCT02385513 and was funded by Gavi, the Vaccine Alliance. Article access can be found here.