Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults

M. J M Bonten; S. M. Huijts; M. Bolkenbaas; C. Webber; S. Patterson; S. Gault; C. H. Van Werkhoven; A. M M Van Deursen; E. A M Sanders; T. J M Verheij; M. Patton; A. McDonough; A. Moradoghli-Haftvani; H. Smith; T. Mellelieu; M. W. Pride; G. Crowther; B. Schmoele-Thoma; D. A. Scott; K. U. Jansen; R. Lobatto; B. Oosterman; N. Visser; E. Caspers; A. Smorenburg; E. A. Emini; W. C. Gruber; D. E. Grobbee

doi:10.1056/NEJMoa1408544

Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults

M. J M Bonten^*, S. M. Huijts, M. Bolkenbaas, C. Webber, S. Patterson, S. Gault, C. H. Van Werkhoven, A. M M Van Deursen, E. A M Sanders, T. J M Verheij, M. Patton, A. McDonough, A. Moradoghli-Haftvani, H. Smith, T. Mellelieu, M. W. Pride, G. Crowther, B. Schmoele-Thoma, D. A. Scott, K. U. JansenR. Lobatto, B. Oosterman, N. Visser, E. Caspers, A. Smorenburg, E. A. Emini, W. C. Gruber, D. E. Grobbee

^*Corresponding author for this work

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Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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-totreat 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.

CONCLUSIONS

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.

Original language	English
Pages (from-to)	1114-1125
Number of pages	12
Journal	New England Journal of Medicine
Volume	372
Issue number	12
DOIs	https://doi.org/10.1056/NEJMoa1408544
Publication status	Published - 1 Jan 2015

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Bonten, M. J. M., Huijts, S. M., Bolkenbaas, M., Webber, C., Patterson, S., Gault, S., Van Werkhoven, C. H., Van Deursen, A. M. M., Sanders, E. A. M., Verheij, T. J. M., Patton, M., McDonough, A., Moradoghli-Haftvani, A., Smith, H., Mellelieu, T., Pride, M. W., Crowther, G., Schmoele-Thoma, B., Scott, D. A., ... Grobbee, D. E. (2015). Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults. New England Journal of Medicine, 372(12), 1114-1125. https://doi.org/10.1056/NEJMoa1408544

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title = "Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults",

abstract = "BACKGROUNDPneumococcal 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.METHODSIn 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.RESULTSIn 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-totreat 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.CONCLUSIONSAmong 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.",

author = "Bonten, {M. J M} and Huijts, {S. M.} and M. Bolkenbaas and C. Webber and S. Patterson and S. Gault and {Van Werkhoven}, {C. H.} and {Van Deursen}, {A. M M} and Sanders, {E. A M} and Verheij, {T. J M} and M. Patton and A. McDonough and A. Moradoghli-Haftvani and H. Smith and T. Mellelieu and Pride, {M. W.} and G. Crowther and B. Schmoele-Thoma and Scott, {D. A.} and Jansen, {K. U.} and R. Lobatto and B. Oosterman and N. Visser and E. Caspers and A. Smorenburg and Emini, {E. A.} and Gruber, {W. C.} and Grobbee, {D. E.}",

year = "2015",

month = jan,

day = "1",

doi = "10.1056/NEJMoa1408544",

language = "English",

volume = "372",

pages = "1114--1125",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

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Bonten, MJM, Huijts, SM, Bolkenbaas, M, Webber, C, Patterson, S, Gault, S, Van Werkhoven, CH, Van Deursen, AMM, Sanders, EAM , Verheij, TJM, 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 2015, 'Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults', New England Journal of Medicine, vol. 372, no. 12, pp. 1114-1125. https://doi.org/10.1056/NEJMoa1408544

TY - JOUR

T1 - Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults

AU - Bonten, M. J M

AU - Huijts, S. M.

AU - Bolkenbaas, M.

AU - Webber, C.

AU - Patterson, S.

AU - Gault, S.

AU - Van Werkhoven, C. H.

AU - Van Deursen, A. M M

AU - Sanders, E. A M

AU - Verheij, T. J M

AU - Patton, M.

AU - McDonough, A.

AU - Moradoghli-Haftvani, A.

AU - Smith, H.

AU - Mellelieu, T.

AU - Pride, M. W.

AU - Crowther, G.

AU - Schmoele-Thoma, B.

AU - Scott, D. A.

AU - Jansen, K. U.

AU - Lobatto, R.

AU - Oosterman, B.

AU - Visser, N.

AU - Caspers, E.

AU - Smorenburg, A.

AU - Emini, E. A.

AU - Gruber, W. C.

AU - Grobbee, D. E.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - BACKGROUNDPneumococcal 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.METHODSIn 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.RESULTSIn 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-totreat 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.CONCLUSIONSAmong 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.

AB - BACKGROUNDPneumococcal 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.METHODSIn 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.RESULTSIn 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-totreat 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.CONCLUSIONSAmong 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.

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Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults

Abstract

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VAB Pneumo project on AOM and Pneumonia indication

Pneumococcal vaccine development

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Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults

Abstract

Access to Document

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Activities

VAB Pneumo project on AOM and Pneumonia indication

Pneumococcal vaccine development

Cite this