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. 2001 Mar;69(3):1593-8.
doi: 10.1128/IAI.69.3.1593-1598.2001.

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

T M Wizemann  1 , J H Heinrichs, J E Adamou, A L Erwin, C Kunsch, G H Choi, S C Barash, C A Rosen, H R Masure, E Tuomanen, A Gayle, Y A Brewah, W Walsh, P Barren, R Lathigra, M Hanson, S Langermann, S Johnson, S Koenig
Affiliations

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

T M Wizemann et al. Infect Immun. 2001 Mar.

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.

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Figures

FIG. 1
FIG. 1
Seroconservation of proteins Sp101 and Sp130 among pneumococcal strains. Whole-cell lysates were prepared from strains with serotypes representative of those contained in current 23-valent carbohydrate vaccines (serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F) or from clinical isolates N4 (serotype 4 strain; source of genomic DNA used in sequencing), SJ2 (serotype 6B), and WU2 and A66 (serotype 3). Proteins in lysates were separated by electrophoresis and immunoblots were probed with rabbit antisera raised against either recombinant Sp101 or Sp130.
FIG. 2
FIG. 2
Immune detection of proteins on the surface of a serotype 4 pneumococcal strain by flow cytometry. Intact pneumococcal cells were probed with antisera generated against recombinant proteins Sp36, Sp91, and Sp130 or with preimmune serum or antiserum specific for the cytosolic chaperone GroEL as negative controls.
FIG. 3
FIG. 3
Immune recognition of pneumococcal vaccine proteins by convalescent-phase sera from patients diagnosed with pneumococcal infections. Recombinant pneumococcal proteins were resolved by polyacrylamide gel electrophoresis and transferred to nitrocellulose membranes. Membranes were probed with convalescent-phase sera obtained from patients recovering from bacteremic pneumococcal pneumonia. Bound antibody was detected with an enzyme-conjugated secondary antibody specific for human immunoglobulin.
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