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

• Type of Material: Article
• Authors: Lisa A. Jackson, Kaiser Permanente Washington Health Research Institute; Hana M. El Sahly, Baylor College of Medicine; Sarah George, St Louis University; Patricia Winokur, University of Iowa; Kathryn Edwards, Vanderbilt University; Rebecca C. Brady, Cincinnati Childrens Hospital Medical Center; Nadine Rouphael, Emory University; Wendy A. Keitel, Baylor College of Medicine; Mark Mulligan, Emory University; Robert L. Burton, University of Alabama Birmingham; Aya Nakamura, Emmes Corporation; Jennifer Ferreria, Emmes Corporation; Moon H. Nahm, University of Alabama Birmingham
• Language: English
• Date: 2018-01-29
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier Ltd
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.vaccine.2017.12.061
• Title of Journal or Parent Work: Vaccine
• ISSN: 0264-410X
• Volume: 36
• Issue: 5
• Start Page: 606
• End Page: 614
• Grant/Funding Information: The network of VTEUs is supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.; This study was conducted by the following Vaccine and Treatment Evaluation Unit (VTEU) sites and collaborating institutions: HHSN272201200005C University of Alabama at Birmingham (contract HHSN272201200005C), Kaiser Permanente Washington (contract HHSN272200800004C), Baylor College of Medicine (contract HHSN272200800002C), St Louis University (contract HHSN272200800003C), Emory University (contract HHSN272201300018I), University of Iowa (contract), Cincinnati Children’s Hospital Medical Center (contract HHSN272200800006C), Vanderbilt University (contract HHSN2722012000031), and the Emmes Corporation (contract HHSN272200800013C).
• Keywords: Pneumococcal vaccine; Immunology; Science & Technology; Medicine, Research & Experimental; Research & Experimental Medicine; Life Sciences & Biomedicine
• Research Categories: Biology, Virology; Health Sciences, Immunology; Biology, Microbiology

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.