Nov 18, 1974 - The specificity of counter-current immunoelectro- phoresis for the detection of pneumococcal antigen in biological fluids was investigated by testing broth cultures of Neisseria meningitidis, Haemophilus influenzae, Staphylococcus aure
common and were the first adjuvant (an immune enhancing vaccine ... lipids, cholesterol, saponins, and antigens which can provide a more robust .... possibly destroying host cells, processes called opsonization and .... While the PCV vaccines can be
Toxoplasma gondii causes severe fetal disease during acute infection in pregnant women, thus demanding early ... techniques such as IgM capture tests increased the sensitivity of these ... IgG avidity was introduced for temporal definition of.
In addition, pulmonary adiaspiromycosis in three European mink from Spain was reported. Key words: Aleutian disease, counter immunoelectrophoresis, ...
We have performed a PsaA conformational analysis both ... Analysis of the heat-induced denaturation demonstrated that Zinc-binding promoted an increase in ...
infection. Three proteins, PcsB, StkP, and PsaA, were evaluated with alum or IC31. ... Supplemental material for this article may be found at http://iai.asm.org/.
This article cites 26 articles, 19 of which can be accessed free. CONTENT ALERTS ... Receive: RSS Feeds, eTOCs, free email alerts (when new ... Downloaded from ..... Amsbaugh, D. F., C. T. Hansen, B. Prescott, P. W. Stashak, D. R. Barthold, ... In A.
study participants were reactive to rapid faecal antigen and serology tests ... tests based on the detection of H. pylori stool antigen [5-6] and serology [7-8].
Oct 30, 1984 - Immunex Corporation, 51 University Street, Seattle, Washington 98101, .... GENTRY et al. ..... EL AYEB M â Int J Peptide Protein Res, 1984, 23, 187-197. ... MINTH CD, BLOOM SR, POLAK JM, DIXON JE â Proc Natl Acad Sci ...
Sep 24, 1982 - disseminated gonococcal infection, one Bartholinitis, three epididymitis, and one a rectal abcess. Patients without gonorrhoea. This included ...
Dr. Sam Sheppard was accused of beating his wife to death. - The show âThe Fugitiveâ was based on his life. He said he was asleep in the living room when his wife was attacked and the intruder knocked him unconscious. - It looked bad for him sinc
Apr 13, 2017 - Receive free email-alerts when new articles cite this article. ... Downloaded from ... protect mice from fatal pneumococcal challenge (11). .... or heavy chain-specific Abs (Southern Biotechnology Associates, Bir- ..... 1945. Preventio
acids 1-288), 3) a proline-rich region (amino acids 289-370),. 4) a choline-binding domain consisting of 9 to 10 twenty- amino-acid repeats (amino acid 371-571) ...
This article cites 46 articles, 29 of which can be accessed free. CONTENT ... http://iai.asm.org/. Downloaded from ..... 2. Effect of mutation of pspA and pspC on intranasal carriage of D39. CBA/N mice were infected with 1. 107 CFU of D39 or its ...
Sep 10, 2012 - Correspondence: Rein Jan Piso, MD, Medizinische Klinik, ... 4 Schuetz P, Albrich WC, Suter I, Hug BL, Christ-Crain M, Holler T, et al. Quality of ...
Jul 20, 2018 - 2010; 14(3):161. https://doi.org/10.1186/cc9013 PMID: 20550728; PubMed Central PMCID: PMCPMC2911716. 23. Arens C, Bajwa SA, Koch C ...
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vanadate, a potent inhibitor of PTP. In contrast, LAR did not dephosphorylate activated STAT3 immunoprecipitated from. LAR knockout VSMC treated with H2O2 ...
Tumor Tissue and Risk of Lethal Prostate Cancer .... defined as PSA above. 0.2 ng/mL after surgery sustained over two measures .... following: microvessel density, that is, the number of vascular .... 1, 0.68 (95% CI, 0.46â1.01), Ptrend Â¼ 0.13,.
Aug 14, 2015 - Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and. Infectious Diseases. Keywords: Binax NOW urine antigen test, DNAaemia, invasive pneumococcal disease, nasopharyngeal swabbing, pneumococcal PCR. Orig
Dietary data was collected by using 24-h recalls combined with a food ... This article is distributed under the terms of the Creative Commons Attribution 4.0 International License .... answer divided into very light (working in a sitting posi- ... be
Oct 22, 2017 - paper. Plasma containing haemolysins agglutinates the test cells because of the anticomplementary nature of the citrate and the bromelin.
Detection of specific antibody has a temporal but not a causal association. â¢ Positive or negative predictive value of result depends on the clinical picture and the.
Pneumococcal protein antigen serology varies with age and may predict antigenic profile of colonizing isolates Azarian T1, Grant LR2, Georgieva M1, Hammitt LL2, Reid R2, Bentley SD3, Goldblatt D4, Santosham M2, Weatherholtz R2, Burbidge P4, Goklish N2, Thompson CM1, Hanage WP1, O’Brien KL2, Lipsitch M1 1 Center for Communicable Disease Dynamics, Department of Epidemiology, T.H. Chan School of Public Health, Harvard University; 2 Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; 3 Wellcome Trust Sanger Institute, Cambridge, UK; 4 Immunobiology Section, Institute of Child Health, University College London, London, UK. Word Count: Abstract: 200 Main test: 3497 References: 37 Lindsay R. Grant [email protected] Maria Georgieva [email protected] Laura Hammitt [email protected] Ray Reid [email protected] Stephen D Bentley [email protected] David Goldblatt [email protected] Mathuram Santosham [email protected] Robert Weatherholtz [email protected] Polly Burbidge [email protected] Novalene Goklish [email protected] Claudette M Thompson [email protected] Bill Hanage [email protected] Kate O’Brien [email protected] Marc Lipsitch [email protected]
Corresponding Author: Taj Azarian, PhD MPH 352.494.2011 Center for Communicable Disease Dynamics, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Suite 506, Boston, MA 02115 [email protected]
43 44 45
and are being investigated as vaccine targets. It is largely unknown whether naturally-
acquired antibodies reduce the risk of colonization with strains expressing a particular
Methods: Serum IgG titers to 28 pneumococcal protein antigens were measured among
242 individuals, aged < 6 months - 78 years in Native American communities between
2007-2009. Nasopharyngeal swabs were collected at least 30 days after serum
collection, and the protein antigen variant in each pneumococcal isolate was determined
using genomic data. We assessed the association between preexisting variant-specific
antibody titers and subsequent carriage of pneumococcus expressing a particular
Results: Antibody titers often increased across pediatric groups before decreasing
among adults. PspA and StkP IgG titers decreased from <6 months to 6-12 months
(p<0.01). Individuals with low titers against Group 3 PspC variants were more likely to
be colonized with pneumococci expressing those variants. For other antigens, variant-
specific IgG titers do not predict colonization with pneumococci expressing particular
Conclusion: We observed an inverse association between variant-specific antibody
concentration and homologous pneumococcal colonization for only one protein. Further
assessment of antibody repertoires may elucidate the nature of anti-pneumococcal
antibody-mediated mucosal immunity while informing future vaccine development.
Background: Several Streptococcus pneumoniae proteins play a role in pathogenesis
Key words: Streptococcus pneumoniae, pneumococci, protein antigens, sera,
immunology, PspC, PspA, vaccine, pilus, antibody
Introduction Current pneumococcal conjugate vaccines have significantly reduced invasive
disease caused by the included Streptococcus pneumoniae (pneumococcal) serotypes.
However, the currently licensed vaccines, PCV-10 and PCV-13, target only 10 or 13 of
the ~90 recognized pneumococcal capsular serotypes. In addition to incomplete
coverage of disease-causing types, significant disadvantages of capsular vaccines
include their production cost, production complexity, and serotype replacement. While
PCV formulations are still an attractive vaccine approach, these limitations have
motivated pursuit of pneumococcal protein antigens as vaccine candidates. Protein-
based vaccines would, in theory, generate robust antibody responses, be efficacious in
young children, and may decrease carriage (1).
Pneumococcal surface protein A (PspA), PspC, pilus (RrgA/B/C), pneumolysin
(Ply) and neuraminidase (NanA) are among the pneumococcal proteins being
investigated for use in vaccine formulations (1). Studies suggest that in some cases
combinations of these proteins may elicit better protection than any of the proteins
themselves (1,2). In humans, antibodies to pneumococcal proteins can be detected
during colonization and natural infection, providing protection from subsequent
colonization and invasive disease (3–8). Virolainen et al. showed that among children
with invasive pneumococcal infections, those with lowest antibody titers to PspA were
infected most frequently with pneumococci (9). However, animal data show that while
antiprotein antibodies are correlated with protection against subsequent challenge, the
mechanism of protection is not necessarily antibody mediated, suggesting antibody
levels may correlate with degree of immune response but not necessarily exclusively
mediate protection. Evidence of variant-specific protection, in which antibodies to a
particular protein antigenic variant correlate with protection against colonization by
homologous pneumococci (i.e. those with that protein variant), would be more strongly
indicative of antiprotein antibodies’ causal role in protection, as has been observed for
Table 2. Protein antigens and variant frequencies identified through genomic analysis of pneumococcal carriage isolates. The antigen name and function are listed with the number of variants tested. Variants with measured titers are specified with an asterisk. Antigen I.
LysM domaincontaining protein Endo-beta-Nacetylglucosaminidase
Choline binding protein Secreted 45 kDa protein Truncated histidine triad protein Part of iron uptake ABC transporter Part of iron uptake ABC transporter Pneumococcal surface adhesin A Conserved hypothetical protein
Figure 1. Pearson correlations of log10 antibody titers for 28 protein antigens clustered heuristically by correlation value. Correlations between normalized antibody titers of protein antigens were clustered using heuristic methods. Protein antigens including multiple variants of the same antigen are labeled on the x- and y- axes, and the heatmap displays the correlation values between antigens. The dendrogram on the left represents the results of the heuristic clustering of correlated antibody titers. Significant correlation between variants of the same antigen was observed as well as high correlation among several antigens, which likely exist on the same genomic background.
Figure 2. Protein antibodies titers by age for variants of PspC, PspA, pilus, and ply. Antibody levels were measured using direct binding electrochemiluminescence-based multiplex assay are expressed as a titer relative to the amount in a reference serum. Structural variants of polymorphic proteins were measured individually and were compared among participant age groups. A.) Variant-specific anti-PspC antibodies to Var-I (ND6053), Var-II (CH2016), Var-III (BR1086), and Var-IV (MD5090). B.) Variantspecific anti-PspA antibodies to Family 1 and Family 2. C.) Anti-pilus antibodies to RrgA-I (TIGR4) and RrgB pilus variants RrgB-I (670-6B), RrgB-II (Taiwan 23F), and RrgB-III (TIGR4). D.) Variant-specific anti-pneumolysin (ply) antibodies to variants I and II.
Figure 3. Protein antibody titers among participants carrying pneumococcal strains with specific polymorphic protein-antigen variants. Serum was collected from participants at enrollment, and nasopharyngeal swabs for pneumococcal carriage detection were collected at least 30 days after serum collection. The protein antigen variant in each pneumococcal isolate was determined using genomic data. Antibody levels were
measured using direct binding electrochemiluminescence-based multiplex assay are expressed as a titer relative to the amount in a reference serum. Structural variants of polymorphic proteins were measured individually. The y-axis represents the variantspecific antibody titers, and the carriage isolate protein antigen variant is specified on the x-axis with labels colored to match the corresponding titers. If susceptibility to a strain possessing a specific variant were observed, the respective antibody titer would be the lowest among all other titers. A) Anti-PspC titers vs. carriage isolate PspC variants I-IV and non-typable. B) Anti-PspC titers vs. carriage isolate PspC var-I and combined varII-IV. C) Anti-PspA Family 1 and Family 2 titers vs. carriage isolate PspA variants Families 1, 2, 3, and unknown. D) Anti-pilus titers vs. carriage isolate RrgB variants I-III and not present.