Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults.
N Engl J Med. 2015 Mar 19;372(12):1114-25.
Bonten MJ1, Huijts SM, Bolkenbaas M, Webber C, Patterson S, Gault S, van Werkhoven CH, van Deursen AM, Sanders EA, Verheij TJ, Patton M, McDonough A, Moradoghli-Haftvani A, Smith H, Mellelieu T, Pride MW, Crowther G, Schmoele-Thoma B, Scott DA, Jansen KU, Lobatto R, Oosterman B, Visser N, Caspers E, Smorenburg A, Emini EA, Gruber WC, Grobbee DE.
1From the Julius Center for Health Sciences and Primary Care (M.J.M.B., S.M.H., M.B., C.H.W., A.M.M.D., T.J.M.V.) and the Department of Medical Microbiology (M.J.M.B., S.M.H., M.B., C.H.W., A.M.M.D., T.J.M.V.), University Medical Center (UMC) Utrecht, and the Department of Immunology and Infectious Diseases, Wilhelmina Children’s Hospital, UMC Utrecht (A.M.M.D., E.A.M.S.), Utrecht, Research Center Linnaeus Institute, Spaarne Hospital, Hoofddorp (A.M.M.D.), and Julius Clinical, Zeist (R.L., B.O., N.V., E.C., A.S., D.E.G.) – all in the Netherlands; Pfizer Vaccine Clinical Research, Maidenhead, United Kingdom (C.W., S.G., M.P., A.M., A.M.-H., H.S., T.M., G.C.); Pfizer Vaccine Clinical Research, Collegeville, PA (S.P., E.A.E.); Pfizer Vaccine Research and Early Development (M.W.P., K.U.J.) and Pfizer Vaccine Clinical Research (D.A.S., E.A.E., W.C.G.), Pearl River, NY; and Pfizer Vaccine Clinical Research, Berlin (B.S.-T.).
Pneumococcal polysaccharide conjugate vaccines prevent pneumococcal disease in infants, but their efficacy against pneumococcal community-acquired pneumonia in adults 65 years of age or older is unknown.
In a randomized, double-blind, placebo-controlled trial involving 84,496 adults 65 years of age or older, we evaluated the efficacy of 13-valent polysaccharide conjugate vaccine (PCV13) in preventing first episodes of vaccine-type strains of pneumococcal community-acquired pneumonia, nonbacteremic and noninvasive pneumococcal community-acquired pneumonia, and invasive pneumococcal disease. Standard laboratory methods and a serotype-specific urinary antigen detection assay were used to identify community-acquired pneumonia and invasive pneumococcal disease.
In the per-protocol analysis of first episodes of infections due to vaccine-type strains, community-acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8 to 62.5), nonbacteremic and noninvasive community-acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2% CI, 14.2 to 65.3), and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8). Efficacy persisted throughout the trial (mean follow-up, 3.97 years). In the modified intention-to-treat analysis, similar efficacy was observed (vaccine efficacy, 37.7%, 41.1%, and 75.8%, respectively), and community-acquired pneumonia occurred in 747 persons in the PCV13 group and 787 persons in placebo group (vaccine efficacy, 5.1%; 95% CI, -5.1 to 14.2). Numbers of serious adverse events and deaths were similar in the two groups, but there were more local reactions in the PCV13 group.
Among older adults, PCV13 was effective in preventing vaccine-type pneumococcal, bacteremic, and nonbacteremic community-acquired pneumonia and vaccine-type invasive pneumococcal disease but not in preventing community-acquired pneumonia from any cause. (Funded by Pfizer; CAPITA ClinicalTrials.gov number NCT00744263.).