scholarly journals Acquired, but Not Innate, Immune Responses to Streptococcus pneumoniae Are Compromised by Neutralization of CD40L

2000 ◽  
Vol 68 (2) ◽  
pp. 511-517 ◽  
Author(s):  
Young-il Hwang ◽  
Moon H. Nahm ◽  
David E. Briles ◽  
David Thomas ◽  
Jeffrey M. Purkerson
Keyword(s):  
Streptococcus Pneumoniae ◽  
Capsular Polysaccharide ◽  
Pneumococcal Infection ◽  
Systemic Infection ◽  
Humoral Response ◽  
Nasal Carriage ◽  
The Elderly ◽  
Antibody Responses ◽  
Capsular Polysaccharides ◽  
Cell Wall Polysaccharides

ABSTRACT Streptococcus pneumoniae is a significant pathogen of young children and the elderly. Systemic infection by pneumococci is a complex process involving several bacterial and host factors. We have investigated the role of CD40L in host defense against pneumococcal infection. Treatment of mice with MR-1 antibody (anti-CD154/CD40L) markedly reduced antibody responses to the pneumococcal protein PspA, elicited by immunization of purified protein or whole bacteria. In mice immunized with whole bacteria, MR-1 treatment reduced antibody responses to capsular polysaccharides but not cell wall polysaccharides. MR-1 did not suppress antibody responses to isolated capsular polysaccharides but did reduce the production of antibody to a capsular polysaccharide-protein conjugate, indicating that when presented in the context of whole bacteria, the humoral response to capsular polysaccharides is partially T-cell dependent. Despite the reduction of the protective humoral responses to pneumococcal infection, administration of MR-1 had no effect on sepsis, lung infection, or nasal carriage in nonimmune mice inoculated with virulent pneumococci. Thus, short-term neutralization of CD40L does not compromise innate host defenses against pneumococcal invasion.

scholarly journals Relationship between Surface Accessibility for PpmA, PsaA, and PspA and Antibody-Mediated Immunity to Systemic Infection by Streptococcus pneumoniae

2005 ◽  
Vol 73 (3) ◽  
pp. 1304-1312 ◽  
Author(s):  
Dennis O. Gor ◽  
Xuedong Ding ◽  
David E. Briles ◽  
Michael R. Jacobs ◽  
Neil S. Greenspan
Keyword(s):  
Streptococcus Pneumoniae ◽  
Capsular Polysaccharide ◽  
Protein A ◽  
Age Groups ◽  
Pneumococcal Infection ◽  
Systemic Infection ◽  
Surface Protein ◽  
Target Antigen ◽  
Age Related ◽  
Type 3

ABSTRACT Antibodies to capsular polysaccharide (PS) are protective against systemic infection by Streptococcus pneumoniae, but the large number of pneumococcal serogroups and the age-related immunogenicity of pure PS limit the utility of PS-based vaccines. In contrast, cell wall-associated proteins from different capsular serotypes can be cross-reactive and immunogenic in all age groups. Therefore, we evaluated three pneumococcal proteins with respect to relative accessibility to antibody, in the context of intact pneumococci, and their ability to elicit protection against systemic infection by encapsulated S. pneumoniae. Sequences encoding pneumococcal surface adhesin A (PsaA), putative protease maturation protein A (PpmA), and the N-terminal region of pneumococcal surface protein A (PspA) from S. pneumoniae strain A66.1 were cloned and expressed in Escherichia coli. The presence of genes encoding PsaA, PpmA, and PspA in 11 clinical isolates was examined by PCR, and the expression of these proteins by each strain was examined by Western blotting with antisera raised to the respective recombinant proteins. We used flow cytometry to demonstrate that PspA was readily detectable on the surface of the pneumococcal strains analyzed, whereas PsaA and PpmA were not. Consistent with these observations, mice with passively or actively acquired antibodies to PspA or type 3 PS were equivalently protected from homologous systemic challenge with type 3 pneumococci, whereas mice with passively or actively acquired antibodies to PsaA or PpmA were not effectively protected. These experiments support the hypothesis that the extent of protection against systemic pneumococcal infection is influenced by target antigen accessibility to circulating host antibodies.

scholarly journals Assignment of Weight-Based Immunoglobulin G1 (IgG1) and IgG2 Units in Antipneumococcal Reference Serum Lot 89-S(F) for Pneumococcal Polysaccharide Serotypes 1, 4, 5, 7F, 9V, and 18C

2005 ◽  
Vol 12 (1) ◽  
pp. 218-223 ◽  
Author(s):  
Daniel J. Sikkema ◽  
Nancy A. Ziembiec ◽  
Thomas R. Jones ◽  
Stephen W. Hildreth ◽  
Dace V. Madore ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Pneumococcal Disease ◽  
Pneumococcal Infection ◽  
Capsular Polysaccharides ◽  
Standardization Method ◽  
Igg2 Antibody ◽  
Reference Serum

ABSTRACT Weight-based assignments for immunoglobulin G1 (IgG1) and IgG2 subclass antibodies to Streptococcus pneumoniae capsular polysaccharides (PnPs) in antipneumococcal standard reference serum lot 89-S (lot 89-S), also known as lot 89-SF, have been determined for serotypes 1, 4, 5, 7F, 9V, and 18C. This extends the usefulness of lot 89-S beyond the IgG1 and IgG2 subclass assignments for serotypes 3, 6B, 14, 19F, and 23F made previously (A. Soininen, H. Kayhty, I. Seppala, and T. Wuorimaa, Clin. Diagn. Lab. Immunol. 5:561-566, 1998) to cover 11 major serotypes associated with the highest percentage of pneumococcal disease worldwide. A method of equivalence of absorbances in enzyme immunosorbent assays was used to determine the IgG1 and IgG2 antibody concentrations for the additional serotypes in lot 89-S, based on the subclass values previously assigned for PnPs serotypes 6B, 14, and 23F. This cross-standardization method assures consistency with previous antibody assignments in that reference serum. The newly assigned subclass values for serotype 9V, and previously assigned values for serotype 14, were used to quantitate PnPs antibodies in sera from adult and pediatric subjects immunized with a pneumococcal conjugate vaccine. There was a predominance of IgG1 anti-PnPs antibodies in pediatric sera and IgG2 anti-PnPs antibodies in the adult sera. The IgG1 and IgG2 subclass assignments for the 11 PnPs serotypes in antipneumococcal standard reference serum lot 89-S are useful for quantitating and characterizing immune responses to pneumococcal infection and vaccination regimens.

scholarly journals Antibody Responses to Capsular Polysaccharide Backbone and O-Acetate Side Groups of Streptococcus pneumoniae Type 9V in Humans and Rhesus Macaques

1998 ◽  
Vol 66 (8) ◽  
pp. 3705-3710 ◽  
Author(s):  
Tessie B. McNeely ◽  
Joan M. Staub ◽  
Cynthia M. Rusk ◽  
Michael J. Blum ◽  
John J. Donnelly
Keyword(s):  
Streptococcus Pneumoniae ◽  
Capsular Polysaccharide ◽  
Rhesus Macaques ◽  
Acute Otitis Media ◽  
Antibody Responses ◽  
Side Chains ◽  
Monkey Model ◽  
Repeat Units ◽  
Pneumococcal Bacteremia ◽  
Infant Rhesus

ABSTRACT Streptococcus pneumoniae is responsible for high rates of pneumococcal bacteremia, meningitis, pneumonia, and acute otitis media worldwide. Protection from disease is conferred by antibodies specific for the polysaccharide (Ps) capsule of the bacteria. Of the four types of group 9 pneumococci, types 9N and 9V cause the most disease, and both types are included in the polyvalent pneumococcal vaccine. The type 9V capsule consists of repeating pentasaccharide units linearly arranged, with an average of 1 to 2 mol of O-acetate side chains per mol of repeat units, added in a complex pattern in which not all repeat units are alike. α-GlcA residues may be O-acetylated in the 2 (17%) or 3 (25%) position and β-ManNAc residues may be O-acetylated in the 4 (6%) or 6 (55%) position. Under certain conditions, the O-acetate side chains are subject to oxidation, which results in subsequent de-O-acetylation of a significant number of the repeat units. This de-O-acetylation could adversely affect the efficacy of a vaccine containing the 9V Ps. A study was undertaken to compare the relative contributions of O-acetate and Ps backbone epitopes in the immune response to S. pneumoniae 9V type-specific Ps. In both an infant rhesus monkey model and humans, antibodies against the non-O-acetylated 9V backbone as well as against O-acetylated 9V Ps were detected. Functional (opsonophagocytic) activity was observed in antisera in which the predominant species of antibody recognized de-O-acetylated 9V Ps. We concluded that the O-acetate side groups, while recognized, are not essential to the ability of the 9V Ps to induce functional antibody responses.

scholarly journals Generation of Antibody Responses to Pneumococcal Capsular Polysaccharides Is Independent of CD1 Expression in Mice

2009 ◽  
Vol 77 (5) ◽  
pp. 1976-1980 ◽  
Author(s):  
Leen Moens ◽  
Axel Jeurissen ◽  
Stefan Nierkens ◽  
Louis Boon ◽  
Luc Van Kaer ◽  
...  
Keyword(s):  
Antibody Response ◽  
The Elderly ◽  
Immunoglobulin M ◽  
Antibody Responses ◽  
Capsular Polysaccharides ◽  
Wild Type ◽  
Igg Antibody ◽  
Antibody Treatment ◽  
Serious Infection ◽  
Protection Against Infection

ABSTRACT Streptococcus pneumoniae is a bacterial microorganism that frequently causes serious infection, particularly in children and the elderly. Protection against infection with S. pneumoniae is based mainly on the generation of antibodies to the pneumococcal capsular polysaccharides (caps-PS), but the mechanisms responsible for the generation of anticapsular antibodies remain incompletely understood. The aim of the present study was to evaluate the role of CD1-restricted T cells in the antibody response to caps-PS. When immunized with Pneumo23, wild-type mice and CD1 knockout mice on BALB/c and C57BL/6 backgrounds generated immunoglobulin M (IgM) and IgG antibody responses to soluble caps-PS that were comparable. Similar results were obtained after immunization with heat-inactivated S. pneumoniae. The IgM and IgG antibody response of wild-type mice to Pneumo23 was not affected by an antagonizing monoclonal anti-CD1 antibody treatment. In summary, our data provide evidence that the antibody response to caps-PS is generated independently of CD1 expression.

scholarly journals Serum immunoglobulins and anti-pneumococcal antibody levels in patients with bronchiectasis of unknown aetiology

2020 ◽  
Vol 19 (2) ◽  
pp. 200-207
Author(s):  
Mustafa Norhazlin ◽  
Asrul Abdul Wahab ◽  
Mohd Faisal Abdul Hamid ◽  
Hamzaini Abdul Hamid ◽  
Husyairi Harunarashid
Keyword(s):  
Streptococcus Pneumoniae ◽  
Specific Antibody ◽  
Capsular Polysaccharide ◽  
Medical Science ◽  
Asian Population ◽  
Immunoglobulin Therapy ◽  
Female Gender ◽  
Total Serum ◽  
Capsular Polysaccharides ◽  
Serum Immunoglobulins

Background: Bronchiectasis is a chronic condition which can result in significant physical and social morbidity. The exact prevalence in Malaysia is unknown although several studies have shown a higher prevalence in the Asian population. Several causative factors have been identified but there are many patients with unknown aetiologies. This study looks into the level of serum immunoglobulins and antipenumococcal antibody in bronchiectasis patients where they were not part of prior routine investigations. Methodology: Four hundred fifteen bronchiectasis patients were screened and 26 patients who fulfilled the inclusion and exclusion criteria were enrolled for this study. The serum immunoglobulins (IgG, IgA and IgM) concentrations were measured using nephelometry and interpreted according to age-matched reference range. The integrity of antibody production against specific antibody to capsular polysaccharides of Streptococcus pneumoniae were assessed using ELISA method and the level of ≥ 10mg/L is considered as reactive. Results: The twenty six bronchiectasis patients have the mean age of 62 years and a predilection of female gender. Majority of patients presented with typical bronchiectasis symptoms which were further supported by radiological findings. One of 26 patients (4%) had low total serum IgG level. The vaccinated group has higher anti-pneumococcal capsular polysaccharide antibody level (median: 224.2 mg/L) compared to the unvaccinated group (median: 100.4 mg/L). However there is no statistical difference between the anti-PCP levels of both groups (p> 0.05). All of the selected patients had reactive specific antibody to capsular polysaccharides of Streptococcus pneumoniae regardless of the vaccination status, which may reflect the natural acquisition of anti-pneumococcal immunity. Conclusion: Although immunoglobulin deficiency is an uncommon aetiological cause of bronchiectasis, the immunoglobulin parameters can be helpful in selecting patients who should receive the appropriate treatment of immunoglobulin therapy for the prevention of subsequent complications and better quality of life. Bangladesh Journal of Medical Science Vol.19(2) 2020 p.200-207

scholarly journals Production of Capsular Polysaccharide ofStreptococcus pneumoniae Type 14 and Its Purification by Affinity Chromatography

2001 ◽  
Vol 67 (2) ◽  
pp. 969-971 ◽  
Author(s):  
Norma Suárez ◽  
Laura Franco Fraguas ◽  
Esther Texeira ◽  
Hugo Massaldi ◽  
Francisco Batista-Viera ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Affinity Chromatography ◽  
Efficient Method ◽  
Capsular Polysaccharide ◽  
Capsular Polysaccharides ◽  
Affinity Adsorbent ◽  
Soybean Lectin

ABSTRACT We describe a rapid and efficient method for producing the capsular polysaccharide of Streptococcus pneumoniae by fermentation on tryptic soy broth and purification of this compound by using immobilized soybean lectin as an affinity adsorbent. In principle, the same strategy can be used to produce purified capsular polysaccharides from other streptococcal serotypes by selecting the appropriate lectin adsorbents.

Serum Antibody Responses of High-Risk Children and Adults to Vaccination with Capsular Polysaccharides of Streptococcus pneumoniae

1981 ◽  
Vol 3 (Supplement_1) ◽  
pp. S168-S178 ◽  
Author(s):  
G. Scott Giebink ◽  
Chap T. Le ◽  
Fernando G. Cosio ◽  
John S. Spika ◽  
Gerald Schiffman
Keyword(s):  
Streptococcus Pneumoniae ◽  
High Risk ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Capsular Polysaccharides ◽  
High Risk Children

scholarly journals Infection with Conditionally Virulent Streptococcus pneumoniae ΔpabStrains Induces Antibody to Conserved Protein Antigens but Does Not Protect against Systemic Infection with Heterologous Strains

2011 ◽  
Vol 79 (12) ◽  
pp. 4965-4976 ◽  
Author(s):  
Suneeta Chimalapati ◽  
Jonathan Cohen ◽  
Emilie Camberlein ◽  
Claire Durmort ◽  
Helen Baxendale ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Capsular Polysaccharide ◽  
Bacterial Pathogen ◽  
Systemic Infection ◽  
Complete Medium ◽  
Protein Antigens ◽  
Live Attenuated Vaccine ◽  
Content Type ◽  
Immunological Responses ◽  
Heterologous Challenge

ABSTRACTAvirulent strains of a bacterial pathogen could be useful tools for investigating immunological responses to infection and potentially effective vaccines. We have therefore constructed an auxotrophic TIGR4 Δpabstrain ofStreptococcus pneumoniaeby deleting thepabBgene Sp_0665. The TIGR4 Δpabstrain grew well in complete medium but was unable to grow in serum unless it was supplemented withpara-aminobenzoic acid (PABA). The TIGR4 Δpabstrain was markedly attenuated in virulence in mouse models ofS. pneumoniaenasopharyngeal colonization, pneumonia, and sepsis. Supplementing mouse drinking water with PABA largely restored the virulence of TIGR4 Δpab. An additional Δpabstrain constructed in the D39 capsular serotype 2 background was also avirulent in a sepsis model. Systemic inoculation of mice with TIGR4 Δpabinduced antibody responses toS. pneumoniaeprotein antigens, including PpmA, PsaA, pneumolysin, and CbpD, but not capsular polysaccharide. Flow cytometry demonstrated that IgG in sera from TIGR4 Δpab-vaccinated mice bound to the surface of TIGR4 and D39 bacteria but not to a capsular serotype 3 strain, strain 0100993. Mice vaccinated with the TIGR4 Δpabor D39 Δpabstrain by intraperitoneal inoculation were protected from developing septicemia when challenged with the homologousS. pneumoniaestrain. Vaccination with the TIGR4 Δpabstrain provided only weak or no protection against heterologous challenge with the D39 or 0100993 strain but did strongly protect against a TIGR4 capsular-switch strain expressing a serotype 2 capsule. The failure of cross-protection after systemic vaccination with Δpabbacteria suggests that parenteral administration of a live attenuated vaccine is not an attractive approach for preventingS. pneumoniaeinfection.

scholarly journals Serum Antibody Responses against Carbapenem-Resistant Klebsiella pneumoniae in Infected Patients

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Kasturi Banerjee ◽  
Michael P. Motley ◽  
Elizabeth Diago-Navarro ◽  
Bettina C. Fries
Keyword(s):  
Klebsiella Pneumoniae ◽  
Capsular Polysaccharide ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Capsular Polysaccharides ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Reactive Properties

ABSTRACT Capsular polysaccharide (CPS) heterogeneity within carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strain sequence type 258 (ST258) must be considered when developing CPS-based vaccines. Here, we sought to characterize CPS-specific antibody responses elicited by CR-Kp-infected patients. Plasma and bacterial isolates were collected from 33 hospital patients with positive CR-Kp cultures. Isolate capsules were typed by wzi sequencing. Reactivity and measures of efficacy of patient antibodies were studied against 3 prevalent CR-Kp CPS types (wzi29, wzi154, and wzi50). High IgG titers against wzi154 and wzi50 CPS were documented in 79% of infected patients. Patient-derived (PD) IgGs agglutinated CR-Kp and limited growth better than naive IgG and promoted phagocytosis of strains across the serotype isolated from their donors. Additionally, poly-IgG from wzi50 and wzi154 patients promoted phagocytosis of nonconcordant CR-Kp serotypes. Such effects were lost when poly-IgG was depleted of CPS-specific IgG. Additionally, mice infected with wzi50, wzi154, and wzi29 CR-Kp strains preopsonized with wzi50 patient-derived IgG exhibited lower lung CFU than controls. Depletion of wzi50 antibodies (Abs) reversed this effect in wzi50 and wzi154 infections, whereas wzi154 Ab depletion reduced poly-IgG efficacy against wzi29 CR-Kp. We are the first to report cross-reactive properties of CPS-specific Abs from CR-Kp patients through both in vitro and in vivo models. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae is a rapidly emerging public health threat that can cause fatal infections in up to 50% of affected patients. Due to its resistance to nearly all antimicrobials, development of alternate therapies like antibodies and vaccines is urgently needed. Capsular polysaccharides constitute important targets, as they are crucial for Klebsiella pneumoniae pathogenesis. Capsular polysaccharides are very diverse and, therefore, studying the host’s capsule-type specific antibodies is crucial to develop effective anti-CPS immunotherapies. In this study, we are the first to characterize humoral responses in infected patients against carbapenem-resistant Klebsiella pneumoniae expressing different wzi capsule types. This study is the first to report the efficacy of cross-reactive properties of CPS-specific Abs in both in vitro and in vivo models.

scholarly journals Immunization with Components of Two Iron Uptake ABC Transporters Protects Mice against Systemic Streptococcus pneumoniae Infection

2001 ◽  
Vol 69 (11) ◽  
pp. 6702-6706 ◽  
Author(s):  
Jeremy S. Brown ◽  
A. David Ogunniyi ◽  
Matthew C. Woodrow ◽  
David W. Holden ◽  
James C. Paton
Keyword(s):  
Streptococcus Pneumoniae ◽  
Abc Transporters ◽  
Iron Uptake ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Systemic Infection ◽  
Antibody Responses ◽  
Protein Vaccine ◽  
Protein Antigens ◽  
Bacterial Cell Membrane

ABSTRACT There has been considerable recent research into protein basedStreptococcus pneumoniae vaccines as alternatives to the existing capsular antigen vaccines. PiuA and PiaA (formerly Pit1A and Pit2A) are recently identified lipoprotein components of S. pneumoniae iron uptake ABC transporters which are required for full virulence and are likely to be expressed on the surface of the bacterial cell membrane. We investigated the efficacy of recombinant PiuA and PiaA proteins at eliciting protective immunity in mice against systemic infection with S. pneumoniae. Both recombinant PiuA and PiaA generated antibody responses that cross-reacted with each other but not with pneumolysin and reacted with identical proteins from nine different S. pneumoniae serotypes. Mice immunized with recombinant PiuA and PiaA were protected against systemic challenge to a degree similar to those immunized with an existing protein vaccine candidate, PdB (a genetically modified pneumolysin toxoid). Immunization with a combination of both PiuA and PiaA resulted in additive protection and was highly protective against systemic infection with S. pneumoniae. PiuA and PiaA are therefore promising additional candidates for a novel S. pneumoniae vaccine using protein antigens.

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