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Chapter 25 : Vaccine-Induced Immunity to Pneumococcal Infection

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Vaccine-Induced Immunity to Pneumococcal Infection, Page 1 of 2

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Abstract:

A consensus of the importance of the bacterial capsule for protective immunity has prevailed from very early on, based on the serotype specificity of the first whole-cell vaccines and soon after that on the protective immunity observed after vaccination with the purified polysaccharide. The evidence of serotype-specific protection against bacteremia in immunocompetent adults, starting approximately 2 weeks after a single dose of the polysaccharide vaccine, is unequivocal based on both clinical trials before vaccine licensure and the subsequent experience with the wide use of the polysaccharide vaccine. Pneumococcal pneumonia was believed to be a major cause of illness and even death in these populations. However, a vaccine effect could not be seen in either of the trials with respect to overall or serotype-specific pneumococcal pneumonia or pneumonia-associated deaths. In view of the importance of pneumonia for children in developing countries, it is regrettable that further studies to confirm or refute these findings have not been conducted in the face of a lack of funding and an expectation of an improved vaccine. In recent studies in Finland almost every child has been shown to have had at least one episode, and many several, of otitis media before the age of 2 years, with pneumococci present in the purulent middle ear fluid in 30% of these cases. The major study to test the protective efficacy of the 7-valent conjugate vaccine was carried out in California, within the framework of the large health insurance plan of Kaiser Permanente.

Citation: Mäkelä P, Käyhty H. 2004. Vaccine-Induced Immunity to Pneumococcal Infection, p 403-420. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch25

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[chapter 2] Venn diagrams of BlastP comparisons of different genomes. The genomes compared in panel A are strain TIGR4, strain 2603 V/R (GBS), and strain SF370 (GAS). Numbers in the intersections represent genes shared in the respective species-to-species (A) or strain-to-strain (B) comparison. The colors represent the genome used as the query in each case. Numbers vary slightly depending on the query because of gene duplications in some strains or species. A BlastP e-value cutoff of 10e was used in each case.

Citation: Mäkelä P, Käyhty H. 2004. Vaccine-Induced Immunity to Pneumococcal Infection, p 403-420. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch25
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[chapter 2] Circular representation of the genomic content of 13 diverse strains compared to the TIGR4 strain genome through CGH on a preliminary microarray. The cDNA microarray consisted of amplicons representing 1,954 of the 2,326 genes from the sequenced strain TIGR4. Results for the competitive hybridization between TIGR4 DNA labeled with Cy3 and the DNA from a single strain labeled with Cy5 are shown in each of the circles. Genes are either (i) present in test strain (white), (ii) absent from test strain (shown in blue for Cy3/Cy5 ratios of 5 to 10 or red for Cy3/Cy5 ratios of more than 10), or (iii) not present on the array and not analyzed (182 genes, 8% of total) (also left in white, so as to focus the discussion on those genes for which a test was performed but no orthologs were detected). The two outermost circles are the predicted genes on the forward and reverse strands, color coded by functional category. The third circle is the analysis; of atypical nucleotide composition; the most atypical regions are displayed in green. The fourth circle is the GC skew analysis; positive values are indicated in yellow, and negative values are in cyan. The next circles on the left diagram correspond to strains MA through MG (outer circle to inner circle). The circles on the right diagram correspond to strains MI through MN.

Citation: Mäkelä P, Käyhty H. 2004. Vaccine-Induced Immunity to Pneumococcal Infection, p 403-420. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch25
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[chapter 5] Structural model of PLY showing the four domains of the proteins and the conserved undecapeptide loop. The region involved in complement activation is marked. The model is based on reference 74.

Citation: Mäkelä P, Käyhty H. 2004. Vaccine-Induced Immunity to Pneumococcal Infection, p 403-420. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch25
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[chapter 6] Predicted structural organization of LytA and its Ch-binding domain. (A) Physicochemical studies suggest the organization of a LytA dimer having four subdomains per monomer, two (N1 and N2) located N terminally and two (C1 and C2) located C terminally. Reprinted from the (69) with permission of the publisher. (B) Stereo ribbon diagram of the dimeric C-LytA with β-strand assignments. The two monomers are differently colored (yellow and cyan). Reprinted from the (14) with permission of the publisher. (C) Ch-binding sites. , ribbon diagram of the C-LytA dimer inscribed into the molecular surface. , stereo diagram of one Ch-binding site where choline is highlighted in orange. Reprinted from (15) with permission of the publisher.

Citation: Mäkelä P, Käyhty H. 2004. Vaccine-Induced Immunity to Pneumococcal Infection, p 403-420. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch25
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[chapter 8] Clonal complexes within the pneumococcal population represented in the MLST database. All isolates in the pneumococcal MLST database (as of September 2003) were displayed as a single eBURST diagram (a population snapshot [17a]). Clusters of linked STs correspond to clonal complexes; single STs differ from all other STs in the population at two or more loci. The areas of the circles representing the individual STs indicate the prevalence of each ST in the current database; STs in blue are the predicted founders of the clonal complex, and those in yellow are founders of subgroups within the clonal complex (17a). For clarity, ST numbers are not shown, except for ST81.

Citation: Mäkelä P, Käyhty H. 2004. Vaccine-Induced Immunity to Pneumococcal Infection, p 403-420. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch25
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[chapter 15] Progression of pneumonia followed by in vivo imaging. Xenogen Imaging System was used to follow the spread of luciferase-bearing pneumococci introduced intranasally. Bacteria descended into the lung by 24 h, spread from one lung to the other by 48 h, and then spread to the bloodstream by 72 h.

Citation: Mäkelä P, Käyhty H. 2004. Vaccine-Induced Immunity to Pneumococcal Infection, p 403-420. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch25
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[chapter 15] Histopathology of three stages of consolidation. Hematoxylin and eosin staining of sections of lung representing the indicated stages of consolidation progressing from engorgement to red to grey hepatization. (Images courtesy of S. Dixon, St. Jude Children's Research Hospital.)

Citation: Mäkelä P, Käyhty H. 2004. Vaccine-Induced Immunity to Pneumococcal Infection, p 403-420. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch25
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[chapter 15] Model of pneumococcal invasion into alveolar epithelial cells. Pneumococci adhere to glycoconjugates on the surfaces of epithelial cells. A second step is required to initiate uptake and transcytosis. In the lung, the second step involves the interaction of choline on the cell wall and CbpA with PAFr. The molecular details of this event are as yet unclear but pneumococci and PAFr colocalize during invasion of type II alveolar cells in vitro. Subsequent to PAFr ligation, bacteria are taken up into a clathrin-coated vesicle that recruits the cytosolic scaffold protein β arrestin. The vesicle then moves across the cell from the apical to basolateral surface. Internalized bacteria do not escape the vesicles. In vitro, bilayers of epithelial and endothelial cells can be crossed by pneumococci in about 9 h.

Citation: Mäkelä P, Käyhty H. 2004. Vaccine-Induced Immunity to Pneumococcal Infection, p 403-420. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch25
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[chapter 16] Gram stain of CSF from a patient with meningitis. A large number of leukocytes surrounded by gram-positive diplococci have accumulated in the fluid. Note that in the fluid environment, few bacteria are effectively phagocytosed. (Photo courtesy of E. Halle, Charité Hospital, Berlin, Germany.)

Citation: Mäkelä P, Käyhty H. 2004. Vaccine-Induced Immunity to Pneumococcal Infection, p 403-420. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch25
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[chapter 18] (a) Antibiotic consumption among the Jewish and Bedouin children <5 years of age in southern Israel, expressed by prescription per 1,000 individuals per year. The data for the Jewish children include all prescriptions in the city of Beer-Sheva for the largest health maintenance organization covering approximately 60% of all children; for the Bedouin children, the data are derived from all prescriptions for the two largest pediatric primary care centers. (b) Proportion of all penicillin-nonsusceptible (Pen-R) middle ear fluid isolated obtained during the years 1998 to 2002 (from children with acute otitis media) that were dually resistant to penicillin and macrolides. (c) Actual and predicted proportions of resistance among invasive isolates derived from population-based surveillance in eight sites around the United States covering approximately 21 million people (81). The symbols represent the actual proportions of strains resistant to both erythromycin and penicillin (●), penicillin only (▄), and erythromycin only (▲). These lines represent the predicted proportions of strains resistant to both erythromycin and penicillin (solid), penicillin alone (dashed) and erythromycin only (dotted).

Citation: Mäkelä P, Käyhty H. 2004. Vaccine-Induced Immunity to Pneumococcal Infection, p 403-420. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch25
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Tables

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TABLE 1

Pneumococcal vaccines at the end of 2003

Citation: Mäkelä P, Käyhty H. 2004. Vaccine-Induced Immunity to Pneumococcal Infection, p 403-420. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch25
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TABLE 2

Summary compilation on the efficacy of the pneumococcal, polysaccharide, and conjugate vaccines in different age groups and clinical entities

Citation: Mäkelä P, Käyhty H. 2004. Vaccine-Induced Immunity to Pneumococcal Infection, p 403-420. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch25

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