Effect of a 2+1 schedule of ten-valent versus 13-valent pneumococcal conjugate vaccine on pneumococcal carriage: Results from a randomised controlled trial in Vietnam

Abstract

Background: Pneumococcal conjugate vaccines (PCVs) generate herd protection by reducing nasopharyngeal (NP) carriage. Two PCVs, PCV10 and PCV13, have been in use for over a decade, yet there are few data comparing their impact on carriage. Here we report their effect on carriage in a 2+1 schedule, compared with each other and with unvaccinated controls.

Methods: Data from four groups within a parallel, open-label randomised controlled trial in Ho Chi Minh City contribute to this article. Three groups were randomised to receive a 2+1 schedule of PCV10 (n = 250), a 2+1 schedule of PCV13 (n = 251), or two doses of PCV10 at 18 and 24 months (controls, n = 197). An additional group (n = 199) was recruited at 18 months to serve as controls from 18 to 24 months. NP swabs collected at 2, 6, 9, 12, 18, and 24 months were analysed (blinded) for pneumococcal carriage. This study aimed to determine if PCV10 and PCV13 have a differential effect on pneumococcal carriage, a secondary outcome of the trial. We also describe the serotype distribution among unvaccinated participants.

Trial registration: ClinicalTrials.gov NCT01953510.

Findings: Compared with unvaccinated controls, a 2+1 schedule of PCV10 reduced PCV10-type carriage by 45-62% from pre-booster through to 24 months of age, and a 2+1 schedule of PCV13 reduced PCV13-type carriage by 36-49% at 12 and 18 months of age. Compared directly with each other, there were few differences between the vaccines in their impact on carriage. Vaccine serotypes accounted for the majority of carriage in unvaccinated participants.

Interpretation: Both PCV10 and PCV13 reduce the carriage of pneumococcal vaccine serotypes. The introduction of either vaccine would have the potential to generate significant herd protection in this population.

Funding: National Health and Medical Research Council of Australia, Bill & Melinda Gates Foundation.

Conflict of interest statement

Declaration of Competing Interest 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. KM has received grant funding for a collaborative study on PCV impact on adult pneumonia from Pfizer. PCV10 vaccine doses were donated by GlaxoSmithKline Biologicals SA. We declare no other competing interests.

Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1

CONSORT diagram. Reasons withdrawn (n = 106): moved away and lost to follow-up (n = 67, 63%); refused a study procedure (n = 19, 18%); 16 (15%) voluntary withdrawal (n = 16, 15%); and other (n = 4, 4%). Reasons excluded: no sample (either participants missed the study visit or attended the visit but had no sample collected, n = 16); insufficient DNA for microarray (n = 24); pneumococcal carriage status could not be determined (n = 6); cultured isolate was irretrievable from freezer storage (n = 1); and excluded as a result of a protocol violation (PCV was administered outside the trial or the sample was collected after administration of PCV, n = 3). Participants who “did not consent to extension” completed the study at 18 months of age, as per the original study design. PCV = pneumococcal conjugate vaccine. PCV10 = ten-valent PCV. PCV13 = 13-valent PCV.

Fig. 2

Pneumococcal carriage prevalence over time. Prevalence (95% CI) of capsular, PCV10-type, PCV13-type, serotype 3/6A/19A, non-PCV10-type, and non-PCV13-type carriage at 2, 6, 9, 12, 18, and 24 months of age, among participants who received a 2+1 schedule (at 2, 4, and 9.5 months of age) of PCV10, a 2+1 schedule of PCV13, or unvaccinated controls. CI = confidence interval. PCV = pneumococcal conjugate vaccine. PCV10 = ten-valent PCV. PCV13 = 13-valent PCV. Control group data come from: Group F (2–12 months); Groups F and G combined (18 months); or Group G (24 months).

Fig. 3

Capsular pneumococcal carriage in unvaccinated participants. The top panel shows the capsular pneumococcal carriage prevalence over time among unvaccinated participants. The bottom panel shows the proportion of carriage at each time point attributable to each of the eight most commonly carried serotypes. Data come from: all groups (2 months); Group F (2–12 months); Groups F and G combined (18 months); or Group G (24 months).