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PMID: 11179332 Published · ppublish English Journal Article

Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae infection.

Infection and immunity ·Vol. 69 ·No. 3 ·2001-03-00 ·Pages 1593-8

Wizemann TM, Heinrichs JH, Adamou JE, Erwin AL, Kunsch C, Choi GH, Barash SC, Rosen CA, Masure HR, Tuomanen E, Gayle A, Brewah YA, Walsh W, Barren P, Lathigra R, Hanson M, Langermann S, Johnson S, Koenig S

Abstract

Microbial targets for protective humoral immunity are typically surface-localized proteins and contain common sequence motifs related to their secretion or surface binding. Exploiting the whole genome sequence of the human bacterial pathogen Streptococcus pneumoniae, we identified 130 open reading frames encoding proteins with secretion motifs or similarity to predicted virulence factors. Mice were immunized with 108 of these proteins, and 6 conferred protection against disseminated S. pneumoniae infection. Flow cytometry confirmed the surface localization of several of these targets. Each of the six protective antigens showed broad strain distribution and immunogenicity during human infection. Our results validate the use of a genomic approach for the identification of novel microbial targets that elicit a protective immune response. These new antigens may play a role in the development of improved vaccines against S. pneumoniae.

MeSH Terms
Amino Acid Sequence Animals Antigens, Bacterial/genetics,therapeutic use Bacterial Vaccines Conserved Sequence Convalescence Female Genomics/methods Humans Mice Mice, Inbred C3H Molecular Sequence Data Pneumococcal Infections/mortality,prevention & control Pneumococcal Vaccines/genetics,therapeutic use Sepsis/mortality,prevention & control Serotyping Streptococcus pneumoniae/classification,genetics,immunology Technology, Pharmaceutical/methods
Chemicals
Antigens, Bacterial Bacterial Vaccines Pneumococcal Vaccines
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Wizemann T M
MedImmune, Inc., Gaithersburg, Maryland 20878, USA.
Heinrichs J H
Adamou J E
Erwin A L
Kunsch C
Choi G H
Barash S C
Rosen C A
Masure H R
Tuomanen E
Gayle A
Brewah Y A
Walsh W
Barren P
Lathigra R
Hanson M
Langermann S
Johnson S
Koenig S
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.69.3.1593-1598.2001
Published
2001-03-00
Pages
1593-8
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC98061
Subset
IM
Databases
GENBANK
AF291695, AF291696, AF291697, AF291698, AF291699
External Links
PubMed source DOI: 10.1128/IAI.69.3.1593-1598.2001 PMC Full Text View journal details
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