Rationale and methods of a randomized controlled trial of immunogenicity, safety and impact on carriage of pneumococcal conjugate and polysaccharide vaccines in infants in Papua New Guinea.

Background: Children in third-world settings including Papua New Guinea (PNG) experience early onset of carriage with a broad range of pneumococcal serotypes, resulting in a high incidence of severe pneumococcal disease and deaths in the first 2 years of life. Vaccination trials in high endemicity settings are needed to provide evidence and guidance on optimal strategies to protect children in these settings against pneumococcal infections.
Methods: This report describes the rationale, objectives, methods, study population, follow-up and specimen collection for a vaccination trial conducted in an endemic and logistically challenging setting in PNG. The trial aimed to determine whether currently available pneumococcal conjugate vaccines (PCV) are suitable for use under PNG's accelerated immunization schedule, and that a schedule including pneumococcal polysaccharide vaccine (PPV) in later infancy is safe and immunogenic in this high-risk population.
Results: This open randomized-controlled trial was conducted between November 2011 and March 2016, enrolling 262 children aged 1 month between November 2011 and April 2014. The participants were randomly allocated (1:1) to receive 10-valent PCV (10vPCV) or 13-valent PCV (13vPCV) in a 1-2-3-month schedule, with further randomization to receive PPV or no PPV at age 9 months, followed by a 1/5 ^th PPV challenge at age 23 months. A total of 1229 blood samples were collected to measure humoral and cellular immune responses and 1238 nasopharyngeal swabs to assess upper respiratory tract colonization and carriage load. Serious adverse events were monitored throughout the study. Of the 262 children enrolled, 87% received 3 doses of PCV, 79% were randomized to receive PPV or no PPV at age 9 months, and 67% completed the study at 24 months of age with appropriate immunization and challenge.
Conclusion: Laboratory testing of the many samples collected during this trial will determine the impact of the different vaccine schedules and formulations on nasopharyngeal carriage, antibody production and function, and immune memory. The final data will inform policy on pneumococcal vaccine schedules in countries with children at high risk of pneumococcal disease by providing direct comparison of an accelerated schedule of 10vPCV and 13vPCV and the potential advantages of PPV following PCV immunization.
Trial Registration: ClinicalTrials.gov CTN NCT01619462, retrospectively registered on May 28, 2012.
Competing Interests: Ethical approval was obtained from the PNG Medical Research Advisory Committee (#11.03) and PNGIMR Institutional Review Board (#1028). The study was conducted according to Declaration of Helsinki International Conference on Harmonization Good Clinical Practice (ICH-GCP) and local ethical guidelines. Assent was sought from pregnant women and their husbands, and informed consent was obtained from the mother at the time of enrolment of the child.Not applicableDL has received support from Pfizer Australia to attend conferences, an honorarium from Merck Vaccines to give a seminar at their offices in Pennsylvania and support from Merck Vaccines to attend a conference; and is an investigator on an investigator-initiated research grant that was funded by Pfizer Australia. PR has received non-financial support from Pfizer, grants from GlaxoSmithKline, grants from Pfizer, and non-financial support from GlaxoSmithKline for work outside the submitted work. WP has received funding from Pfizer Australia to attend a conference. AVDB was previously an employee of Janssen Pharmaceuticals, Johnson and Johnson. LAK has received educational grants and travel support from Pfizer and GSK to attend conferences, is an investigator on an investigator-initiated research grant funded by Pfizer Australia, and is an inventor on patents for a pneumococcal protein vaccine antigen. All other authors declare no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.