Effect of Different Schedules of Ten-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Carriage in Vietnamese Infants: Results From a Randomised Controlled Trial

Abstract

Background: WHO recommends a three-dose infant pneumococcal vaccine (PCV) schedule administered as a two-dose primary series with a booster (2+1) or as a three-dose primary series (3+0). Data on carriage impacts of these and further reduced PCV schedules are needed to inform PCV strategies. Here we evaluate the effect of four different PCV10 schedules on nasopharyngeal carriage.

Methods: Participants within an open-label, randomised controlled trial in Ho Chi Minh City, Vietnam, were allocated to receive PCV10 in a 3+1 (2, 3, 4, 9 months, n=152), 3+0 (2, 3, 4 months, n=149), 2+1 (2, 4, 9.5 months, n=250) or novel two-dose (2, 6 months, n=202) schedule, or no infant doses of PCV (two control groups, n=197 and n=199). Nasopharyngeal swabs collected between 2 and 24 months were analysed (blinded) for pneumococcal carriage and serotypes.

Findings: Pneumococcal carriage prevalence was low (10·6-14·1% for vaccine-type (VT) at 12-24 months in unvaccinated controls). All four PCV10 schedules reduced VT carriage compared with controls (the 2+1 schedule at 12, 18, and 24 months; the 3+1 and two-dose schedules at 18 months; and the 3+0 schedule at 24 months), with reductions of 40·1% to 64·5%. There were no differences in VT carriage prevalence at 6 or 9 months comparing three-dose and two-dose primary series, and no differences at 12, 18, or 24 months when comparing schedules with and without a booster dose.

Interpretation: In Vietnamese children with a relatively low pneumococcal carriage prevalence, 3+1, 2+1, 3+0 and two-dose PCV10 schedules were effective in reducing VT carriage. There were no discernible differences in the effect on carriage of the WHO-recommended 2+1 and 3+0 schedules during the first two years of life.

Trial Registration Details: The trial is registered at ClinicalTrials.gov, number NCT01953510.

Funding Information: This work was supported by the National Health and Medical Research Council of Australia (grant number 566792) and the Bill & Melinda Gates Foundation (grant number OPP1116833). PCV10 vaccine doses were donated by GlaxoSmithKline Biological SA.

Declaration of Interests: The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: All authors except JB and JH received salary support from National Health and Medical Research Council of Australia (NHMRC) and/or Bill & Melinda Gates Foundation grants. PCV10 vaccine doses were donated by GlaxoSmithKline Biologicals SA. KM, CS, and CN are investigators on a clinical research collaboration with Pfizer for a separate study. CS, KM and CN are investigators on a Merck Investigator Studies Program grant funded by MSD on pneumococcal serotype epidemiology in children. EMD is currently employed by Pfizer. We declare no other competing interests.

Ethics Approval Statement: Ethical approval was obtained from the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research, Australia, and the Ministry of Health Ethics Committee, Vietnam.

Keywords: Pneumococcal conjugate vaccine, infant vaccination schedules, pneumococcal carriage