Identification of the Smallest Structure Capable of Evoking Opsonophagocytic Antibodies against Streptococcus pneumoniae Type 14

ABSTRACT Synthetic overlapping oligosaccharide fragments of Streptococcus pneumoniae serotype 14 capsular polysaccharide (Pn14PS), {6)-[β-d-Galp-(1→4)-]β-d-GlcpNAc-(1→3)-β-d-Galp-(1→4)-β-d-Glcp-(1→}n, were conjugated to CRM197 protein and injected into mice to determine the smallest immunogenic structure. The resulting antibodies were then tested for Pn14PS specificity and for their capacity to promote the phagocytosis of S. pneumoniae type 14 bacteria. Earlier studies have reported that the oligosaccharide corresponding to one structural repeating unit of Pn14PS, i.e., Gal-Glc-(Gal-)GlcNAc, induces a specific antibody response to Pn14PS. The broader study described here, which evaluated 16 oligosaccharides, showed that the branched trisaccharide element Glc-(Gal-)GlcNAc is essential in inducing Pn14PS-specific antibodies and that the neighboring galactose unit at the nonreducing end contributes clearly to the immunogenicity of the epitope. Only the oligosaccharide conjugates that produce antibodies recognizing Pn14PS were capable of promoting the phagocytosis of S. pneumoniae type 14. In conclusion, the branched tetrasaccharide Gal-Glc-(Gal-)GlcNAc may be a serious candidate for a synthetic oligosaccharide conjugate vaccine against infections caused by S. pneumoniae type 14.

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Nature and Specificity of the Required Protective Immune Response That Develops Postchallenge in Mice Vaccinated with the 19-Kilodalton Fragment of Plasmodium yoelii Merozoite Surface Protein 1

Infection and Immunity ◽

10.1128/iai.70.11.6013-6020.2002 ◽

2002 ◽

Vol 70 (11) ◽

pp. 6013-6020 ◽

Cited By ~ 11

Author(s):

Jiraprapa Wipasa ◽

Huji Xu ◽

Morris Makobongo ◽

Michelle Gatton ◽

Anthony Stowers ◽

...

Keyword(s):

Immune Response ◽

Antibody Response ◽

Specific Antibody ◽

Natural Infection ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Plasmodium Yoelii ◽

Specific Antibody Response ◽

Specific Antibodies ◽

Merozoite Surface Protein 1

ABSTRACT Immunity induced by the 19-kDa fragment of Plasmodium yoelii merozoite surface protein 1 (MSP119) is dependent on high titers of specific antibodies present at the time of challenge and a continuing active immune response postinfection. However, the specificity of the active immune response postinfection has not been defined. In particular, it is not known whether anti-MSP119 antibodies that arise following infection alone are sufficient for protection. We developed systems to investigate whether an MSP119-specific antibody response alone both prechallenge and postchallenge is sufficient for protection. We were able to exclude antibodies with other specificities, as well as any contribution of MSP119-specific CD4+ T cells acting independent of antibody, and we concluded that an immune response focused solely on MSP119-specific antibodies is sufficient for protection. The data imply that the ability of natural infection to boost an MSP119-specific antibody response should greatly improve vaccine efficacy.

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Co-colonization by Haemophilus influenzae with Streptococcus pneumoniae enhances pneumococcal-specific antibody response in young children

Vaccine ◽

10.1016/j.vaccine.2013.11.096 ◽

2014 ◽

Vol 32 (6) ◽

pp. 706-711 ◽

Cited By ~ 11

Author(s):

Qingfu Xu ◽

Michael E. Pichichero

Keyword(s):

Streptococcus Pneumoniae ◽

Young Children ◽

Antibody Response ◽

Haemophilus Influenzae ◽

Specific Antibody ◽

Specific Antibody Response

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Oral Immunization with F4 Fimbriae and CpG Formulated with Carboxymethyl Starch Enhances F4-Specific Mucosal Immune Response and Modulates Th1 and Th2 Cytokines in Weaned Pigs

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j30w32 ◽

2012 ◽

Vol 15 (5) ◽

pp. 642 ◽

Cited By ~ 12

Author(s):

Benjamin Delisle ◽

Carmen Calinescu ◽

Mircea Alexandru Mateescu ◽

John Morris Fairbrother ◽

Eric Nadeau

Keyword(s):

Antibody Response ◽

Specific Antibody ◽

Subunit Vaccine ◽

Cytokine Production ◽

Oral Dosage ◽

Weaned Pigs ◽

Specific Antibody Response ◽

Specific Antibodies ◽

Carboxymethyl Starch ◽

Ifn Γ

Purpose. F4 fimbriae are a potential candidate for an oral subunit vaccine for prevention of post-weaning diarrhea in swine due to infection with F4-positive enterotoxigenic Escherichia coli. However, large quantities of F4 fimbriae are required to induce a specific antibody response. The aim of the present study was to evaluate the effect of supplementation of F4 fimbriae with Cytosine-phosphate-Guanosine-oligodeoxynucleotide (CpG-A D19) or with complete cholera toxin (CT) as adjuvants on the F4-specific antibody response and cytokine production in weaned pigs following oral administration of F4 fimbrial antigen formulated with Carboxymethyl Starch (CMS). Methods. Oral dosage forms of F4 fimbriae alone or supplemented with CpG-A D19 or with CT were formulated with CMS as monolithic tablets, obtained by direct compression, and administered to weaned pigs. Blood and faecal samples were collected to determine the systemic and mucosal immune status of animals at various times until necropsy. During necropsy, contents of the jejunum and ileum were collected for determination of mucosal F4 specific antibodies. Segments of jejunum and ileum were also used to measure mRNA cytokine production. Results. The presence of CpG in the formulation of the fimbriae significantly increased F4-specific immunoglobulin (Ig) IgM and IgG levels in intestinal secretions, and enhanced Th1 (Interferon-gamma / IFN-γ, Tumour Necrosis Factor-alpha / TNF-α, Interleukin-12p40 / IL-12p40, IL-1β) and Th2 (IL-4, IL-6) cytokine production in intestinal tissues. Supplementation with CT did not result in induction of F4-specific antibodies in secretions, although a significant Th1 response (IFN-α, IFN-γ, IL-18) was detected in tissues. Neither F4-specific systemic antibodies, nor intestinally secreted IgA were detected throughout the immunization trial for all groups. Conclusions. CpG-A D19 appeared to be a promising adjuvant for an oral F4 subunit vaccine formulated with CMS excipient as monolithic tablets. This matrix afforded gastro-protection and delivered the F4 fimbriae at their intestinal sites. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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A Peptide Mimotope of Type 8 Pneumococcal Capsular Polysaccharide Induces a Protective Immune Response in Mice

Infection and Immunity ◽

10.1128/iai.73.1.325-333.2005 ◽

2005 ◽

Vol 73 (1) ◽

pp. 325-333 ◽

Cited By ~ 44

Author(s):

Ulrike K. Buchwald ◽

Andrew Lees ◽

Michael Steinitz ◽

Liise-anne Pirofski

Keyword(s):

At Risk ◽

Antibody Response ◽

Specific Antibody ◽

Capsular Polysaccharide ◽

Immunoglobulin A ◽

Phage Display Library ◽

Specific Antibody Response ◽

Significant Prolongation ◽

Peptide Mimotopes ◽

Patients At Risk

ABSTRACT Increasing antibiotic resistance and a rising patient population at risk for infection due to impaired immunity underscore the importance of vaccination against pneumococci. However, available capsular polysaccharide vaccines are often poorly immunogenic in patients at risk for pneumococcal disease. The goal of this study was to explore the potential of peptide mimotopes to function as alternative vaccine antigens to elicit a type-specific antibody response to pneumococci. We used a human monoclonal immunoglobulin A (IgA) antibody (NAD) to type 8 Streptococcus pneumoniae capsular polysaccharide (type 8 PS) to screen a phage display library, and the phage PUB1 displaying the peptide FHLPYNHNWFAL was selected after three rounds of biopanning. Inhibition studies with phage-displayed peptide or the peptide PUB1 and type 8 PS showed that PUB1 is a mimetic of type 8 PS. PUB1 conjugated to tetanus toxoid (PUB1-TT) induced a type 8 PS-specific antibody response in BALB/c mice, further defining it as a mimotope of type 8 PS. The administration of immune sera obtained from PUB1-TT-immunized mice earlier (days 14 and 21) and later (days 87 and 100) after primary and reimmunization resulted in a highly significant prolongation of the survival of naive mice after pneumococcal challenge compared to controls. The survival of PUB1-TT-immunized mice was also prolonged after pneumococcal challenge nearly 4 months after primary immunization. The efficacy of PUB1-TT-induced immune sera provides proof of principle that a mimotope-induced antibody response can protect against pneumococci and suggests that peptide mimotopes selected by type-specific human antibodies could hold promise as immunogens for pneumococci.

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Class-Specific Antibody Response to Haemophilus influenzae Type b Capsular Polysaccharide Vaccine

The Journal of Infectious Diseases ◽

10.1093/infdis/148.4.767 ◽

1983 ◽

Vol 148 (4) ◽

pp. 767-767 ◽

Cited By ~ 11

Author(s):

H. Kayhty ◽

R. Schneerson ◽

A. Sutton

Keyword(s):

Antibody Response ◽

Haemophilus Influenzae ◽

Specific Antibody ◽

Capsular Polysaccharide ◽

Polysaccharide Vaccine ◽

Haemophilus Influenzae Type ◽

Haemophilus Influenzae Type B ◽

Type B ◽

Specific Antibody Response

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Class-specific antibody response to group B Neisseria meningitidis capsular polysaccharide: use of polylysine precoating in an enzyme-linked immunosorbent assay.

Infection and Immunity ◽

10.1128/iai.38.3.1203-1207.1982 ◽

1982 ◽

Vol 38 (3) ◽

pp. 1203-1207 ◽

Cited By ~ 30

Author(s):

M Leinonen ◽

C E Frasch

Keyword(s):

Antibody Response ◽

Neisseria Meningitidis ◽

Immunosorbent Assay ◽

Specific Antibody ◽

Capsular Polysaccharide ◽

Enzyme Linked Immunosorbent Assay ◽

Specific Antibody Response ◽

Group B

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Antibodies to Streptococcus pneumoniae Capsular Polysaccharide Enhance Pneumococcal Quorum Sensing

mBio ◽

10.1128/mbio.00176-11 ◽

2011 ◽

Vol 2 (5) ◽

Cited By ~ 22

Author(s):

Masahide Yano ◽

Shruti Gohil ◽

J. Robert Coleman ◽

Catherine Manix ◽

Liise-anne Pirofski

Keyword(s):

Monoclonal Antibodies ◽

Streptococcus Pneumoniae ◽

Quorum Sensing ◽

Direct Effect ◽

Pneumococcal Disease ◽

Effector Cell ◽

Capsular Polysaccharide ◽

Genetic Exchange ◽

Content Type ◽

Specific Antibodies

ABSTRACTThe use of pneumococcal capsular polysaccharide (PPS)-based vaccines has resulted in a substantial reduction in invasive pneumococcal disease. However, much remains to be learned about vaccine-mediated immunity, as seven-valent PPS-protein conjugate vaccine use in children has been associated with nonvaccine serotype replacement and 23-valent vaccine use in adults has not prevented pneumococcal pneumonia. In this report, we demonstrate that certain PPS-specific monoclonal antibodies (MAbs) enhance the transformation frequency of two differentStreptococcus pneumoniaeserotypes. This phenomenon was mediated by PPS-specific MAbs that agglutinate but do not promote opsonic effector cell killing of the homologous serotypeinvitro. Compared to the autoinducer, competence-stimulating peptide (CSP) alone, transcriptional profiling of pneumococcal gene expression after incubation with CSP and one such MAb to the PPS of serotype 3 revealed changes in the expression of competence (com)-related and bacteriocin-like peptide (blp) genes involved in pneumococcal quorum sensing. This MAb was also found to induce a nearly 2-fold increase in CSP2-mediated bacterial killing or fratricide. These observations reveal a novel, direct effect of PPS-binding MAbs on pneumococcal biology that has important implications for antibody immunity to pneumococcus in the pneumococcal vaccine era. Taken together, our data suggest heretofore unsuspected mechanisms by which PPS-specific antibodies could affect genetic exchange and bacterial viability in the absence of host cells.IMPORTANCECurrent thought holds that pneumococcal capsular polysaccharide (PPS)-binding antibodies protect against pneumococcus by inducing effector cell opsonic killing of the homologous serotype. While such antibodies are an important part of how pneumococcal vaccines protect against pneumococcal disease, PPS-specific antibodies that do not exhibit this activity but are highly protective against pneumococcus in mice have been identified. This article examines the effect of nonopsonic PPS-specific monoclonal antibodies (MAbs) on the biology ofStreptococcus pneumoniae. The results showed that in the presence of a competence-stimulating peptide (CSP), such MAbs increase the frequency of pneumococcal transformation. Further studies with one such MAb showed that it altered the expression of genes involved in quorum sensing and increased competence-induced killing or fratricide. These findings reveal a novel, previously unsuspected mechanism by which certain PPS-specific antibodies exert a direct effect on pneumococcal biology that has broad implications for bacterial clearance, genetic exchange, and antibody immunity to pneumococcus.

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