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PMID: 18166586 Published · ppublish English Journal Article

Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies.

The Journal of experimental medicine ·Vol. 205 ·No. 1 ·2008-01-21 ·Pages 117-31

Giefing C, Meinke AL, Hanner M, Henics T, Bui MD, Gelbmann D, Lundberg U, Senn BM, Schunn M, Habel A, Henriques-Normark B, Ortqvist A, Kalin M, von Gabain A, Nagy E

Abstract

Pneumococcus is one of the most important human pathogens that causes life-threatening invasive diseases, especially at the extremities of age. Capsular polysaccharides (CPSs) are known to induce protective antibodies; however, it is not feasible to develop CPS-based vaccines that cover all of the 90 disease-causing serotypes. We applied a genomic approach and described the antibody repertoire for pneumococcal proteins using display libraries expressing 15-150 amino acid fragments of the pathogen's proteome. Serum antibodies of exposed, but not infected, individuals and convalescing patients identified the ANTIGENome of pneumococcus consisting of approximately 140 antigens, many of them surface exposed. Based on several in vitro assays, 18 novel candidates were preselected for animal studies, and 4 of them showed significant protection against lethal sepsis. Two lead vaccine candidates, protein required for cell wall separation of group B streptococcus (PcsB) and serine/threonine protein kinase (StkP), were found to be exceptionally conserved among clinical isolates (>99.5% identity) and cross-protective against four different serotypes in lethal sepsis and pneumonia models, and have important nonredundant functions in bacterial multiplication based on gene deletion studies. We describe for the first time opsonophagocytic killing activity for pneumococcal protein antigens. A vaccine containing PcsB and StkP is intended for the prevention of infections caused by all serotypes of pneumococcus in the elderly and in children.

MeSH Terms
Adult Amino Acids/chemistry Animals Antibodies Antigens, Bacterial/chemistry Child Epitopes/chemistry Humans Immunoglobulin A/chemistry Immunoglobulin G/chemistry Mice Middle Aged Pneumococcal Infections/prevention & control Pneumococcal Vaccines/chemistry Polysaccharides/chemistry Streptococcus pneumoniae/genetics,immunology
Chemicals
Amino Acids Antibodies Antigens, Bacterial Epitopes Immunoglobulin A Immunoglobulin G Pneumococcal Vaccines Polysaccharides
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Giefing Carmen
Intercell AG, 1030 Vienna, Austria.
Meinke Andreas L
Hanner Markus
Henics Tamás
Bui Minh Duc
Gelbmann Dieter
Lundberg Urban
Senn Beatrice M
Schunn Michael
Habel Andre
Henriques-Normark Birgitta
Ortqvist Ake
Kalin Mats
von Gabain Alexander
Nagy Eszter
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
1540-9538
DOI
10.1084/jem.20071168
Published
2008-01-21
Epub
2007-00-31
Pages
117-31
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2234372
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20071168 PMC Full Text View journal details
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