Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae infection.
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.
Wizemann
T M
TM
MedImmune, Inc., Gaithersburg, Maryland 20878, USA.
Heinrichs
J H
JH
Adamou
J E
JE
Erwin
A L
AL
Kunsch
C
C
Choi
G H
GH
Barash
S C
SC
Rosen
C A
CA
Masure
H R
HR
Tuomanen
E
E
Gayle
A
A
Brewah
Y A
YA
Walsh
W
W
Barren
P
P
Lathigra
R
R
Hanson
M
M
Langermann
S
S
Johnson
S
S
Koenig
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000627:therapeutic use; D001428:Bacterial Vaccines; D017124:Conserved Sequence; D003289:Convalescence; D005260:Female; D023281:Genomics / Q000379:methods*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D011008:Pneumococcal Infections / Q000401:mortality / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000235:genetics / Q000627:therapeutic use*; D018805:Sepsis / Q000401:mortality / Q000517:prevention & control; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000235:genetics* / Q000276:immunology; D013678:Technology, Pharmaceutical / Q000379:methods*
D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D022242:Pneumococcal Vaccines