Randomized clinical trial of a single versus a double dose of 13-valent pneumococcal conjugate vaccine in adults 55 through 74 years of age previously vaccinated with 23-valent pneumococcal polysaccharide vaccine

Abstract

Introduction: In older adults, prior administration of 23-valent pneumococcal polysaccharide vaccine (PPSV23) blunts the opsonophagocytic antibody (OPA) response to subsequent administration of 13-valent pneumococcal conjugate vaccine (PCV13). To determine whether a higher dose of PCV13 could mitigate this effect in adults 55 through 74 years of age, we compared OPA responses to a double dose of PCV13 in persons previously vaccinated with PPSV23 with responses to a single dose of PCV13 in previously vaccinated persons, and with a single dose in PPSV23 naïve persons.

Methods: Subjects previously vaccinated with PPSV23 were randomly assigned to receive either a single injection or two concurrent injections of 0.5 mL PCV13. Naïve subjects received a single injection of 0.5 mL PCV13. Serotype-specific OPA responses to 12 of the PCV13 serotypes were assessed on samples collected on Day 29 and Day 181. Comparisons of the OPA titers between study groups were based on the lower bound of the 95% confidence interval of the log geometric mean ratio to define superiority (>1) and non-inferiority (>0.5).

Results: At Day 29, the OPA responses to one dose in previously vaccinated (n = 284) versus one dose in naïve subjects (n = 311) achieved the threshold for non-inferiority for only 3 of the 12 serotypes. In previously vaccinated subjects, responses to a double dose (n = 288) versus a single dose met the threshold for superiority for 7 serotypes. The responses to a double dose in previously vaccinated subjects versus a single dose in naïve subjects met the threshold for non-inferiority for 9 serotypes.

Conclusions: There is a dose response to PCV13 in older adults and the higher response to a double dose in previously vaccinated adults is non-inferior to that of a single dose in naïve adults for 9 of the 12 PCV13 serotypes evaluated.

Trial registration: ClinicalTrials.gov NCT01654263.

Keywords: Pneumococcal vaccine.

Conflict of interest statement

Conflict of Interest Disclosures: The University of Alabama at Birmingham (UAB) has IP rights to several reagents developed in M.H.N.’s laboratory, and M.H.N. and R.L.B. are UAB employees. M.H.N and R.L.B. declare no other conflicts of interest. RB reports grant funding from Pfizer for projects not related to this study.

Other co-authors reported no conflicts of interest.

Copyright © 2018 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Comparison of serotype specific geometric mean ratios at Day 29, Group IIA (previously vaccinated, 0.5 mL PCV13) versus Group I (naïve, 0.5 mL PCV13), overall (A) and by age group (B).

Figure 2

Comparison of serotype specific geometric mean ratios at Day 29, Group IIB (previously vaccinated, 1.0 mL PCV13) versus Group IIA (previously vaccinated, 0.5 mL PCV13), overall (A) and by age group (B).

Figure 3

Comparison of serotype specific geometric mean ratios at Day 29, Group IIB (previously vaccinated, 1.0 mL PCV13) versus Group I (naïve, 0.5 mL PCV13), overall (A) and by age group (B).