Protective efficacy of mouse serum to the N-propionyl derivative of meningococcal group B polysaccharide

Ashton, F. E.; Ryan, J. A.; Michon, Francis; Jennings, Harold J.

doi:10.1016/0882-4010(89)90087-9

Cited by 38 publications

(20 citation statements)

References 11 publications

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“…These antibodies also elicited complement-mediated bactericidal activity against the group B meningococcus. Our data corroborate results of previous studies conducted with a similar immunogen (2,19). This places this immunogen as a potential candidate vaccine to prevent group B meningococcal disease or to obtain selected antibodies to be used for treatment of individuals infected by the bacteria.…”

Section: Discussionsupporting

confidence: 90%

Activity and Cross-Reactivity of Antibodies Induced in Mice by Immunization with a Group B Meningococcal Conjugate

Coquillat

Bruge²,

Danve³

et al. 2001

Infect Immun

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The capsular polysaccharide of group B Neisseria meningitidis is composed of a linear homopolymer of ␣(2-8) N-acetyl neuraminic acid or polysialic acid (PSA) that is also carried by isoforms of the mammalian neural cell adhesion molecule (NCAM), which is especially expressed on brain cells during development. Here we analyzed the ability of antibodies induced by the candidate vaccine N-propionyl polysaccharide tetanus toxoid conjugate to recognize PSA-NCAM. We hyperimmunized mice to produce a pool of antisera and a series of immunoglobulin G monoclonal antibodies and evaluated their self-reactivity profile by using a battery of tests (immunoprecipitation, immunoblotting, and immunofluorescence detection on live cells and human tissue sections) chosen for their sensitivity and specificity to detect PSA-NCAM in various environments. We also searched for the effects of the vaccine-induced antibodies in two functional assays involving cell lysis or cell migration. Although they were highly bactericidal, all the antibodies tested showed very low or no recognition of PSA-NCAM, in contrast to PSA-specific monoclonal antibodies used as controls. Different patterns of crossreactions were revealed by the tests used, likely due to affinity and specificity differences among the populations of induced antibodies. Furthermore, neither cell lysis nor perturbation of migration was observed in the presence of the tested antibodies. Importantly, we showed that whereas enzymatic removal of PSA groups from the surfaces of live cells perturbed their migration, blocking them with PSA-specific antibodies was not functionally detrimental. Taken together, our data indicated that this candidate vaccine induced antibodies that could not demonstrate an immunopathologic effect.

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Section: Discussionsupporting

confidence: 90%

Activity and Cross-Reactivity of Antibodies Induced in Mice by Immunization with a Group B Meningococcal Conjugate

Coquillat

Bruge²,

Danve³

et al. 2001

Infect Immun

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“…CPS structure modifications have enhanced immunogenicity and have altered or eliminated epitopes that evoke antibodies crossreactive with host tissue (27,28). Several years ago, investigators substituted type 14 pneumococcal CPS for the structurally similar (29) GBS type III CPS in a vaccine.…”

Section: Discussionmentioning

confidence: 99%

Rational chemical design of the carbohydrate in a glycoconjugate vaccine enhances IgM-to-IgG switching

Guttormsen

Paoletti²,

Mansfield³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Many pathogens are sheltered from host immunity by surface polysaccharides that would be ideal as vaccines except that they are too similar to host antigens to be immunogenic. The production of functional IgG is a desirable response to vaccines; because IgG is the only isotype that crosses the placenta, it is of particular importance in maternal vaccines against neonatal disease due to group B Streptococcus (GBS). Clinical studies found a substantially lower proportion of IgG-relative to IgM-among antibodies elicited by conjugates prepared with purified GBS type V capsular polysaccharide (CPS) than among those evoked by CPSs of other GBS serotypes. The epitope specificity of IgG elicited in humans by a conjugate prepared with type V CPS is for chemically desialylated type V CPS (dV CPS). We studied desialylation as a mechanism for enhancing the ability of type V CPS to induce IgM-to-IgG switching. Desialylation did not affect the structural conformation of type V CPS. Rhesus macaques, whose isotype responses to GBS conjugates match those of humans, produced functionally active IgG in response to a dV CPS-tetanus toxoid conjugate (dV-TT), and 98% of neonatal mice born to dams vaccinated with dV-TT survived lethal challenge with viable GBS. Targeted chemical engineering of a carbohydrate to create a molecule less like host self may be a rational approach for improving other glycoconjugates.C apsular polysaccharides (CPSs) dominate the surface of some bacteria and are the major target of the immune system's attack, which primarily involves antibodies, complement, and phagocytic cells. CPSs are considered T cell-independent antigens; their use in vaccines has been optimal only with protein-carrier chemical conjugation, which elicits T cell help for B cells recognizing the carbohydrate, with consequent isotype switching from IgM to IgG (1). Successful glycoconjugate vaccines have been developed against Haemophilus influenzae type b (2) and several serogroups of Streptococcus pneumoniae (3) and Neisseria meningitidis (4). However, the human immune system sometimes fails to mount an adaptive immune response to microbial CPS because of great structural similarity of the CPS to the host's own cells. For example, the ␣-2,8-linked sialic acid homopolymeric capsule of serogroup B meningococci structurally resembles saccharides on human neural cell adhesion molecules (5) and oligosaccharides on fetal tissues (6). Likewise, the hyaluronic acid capsule of group A Streptococcus is identical to carbohydrate structures on human tissue (7). Humans do not respond with antibodies to these two molecules, presumably because such a response would generate autoimmunity.Group B Streptococcus (GBS) is a major cause of serious infection in neonates and the elderly (8). Of the 10 identified serotypes (9, 10), five (Ia, Ib, II, III, and V) are commonly associated with human disease. Antibodies to the CPSs of these serotypes are protective against neonatal infection and are acquired by the neonate through transplacental passage of CPS-specifi...

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“…Our data show that anti-NMGB Ab could be identified in immune mouse sera after immunizing with Naid60-KLH, Naid60-scFv, or F(abЈ) 2 of Naid60 and that anti-NMGB Ab titers were boosted with injection number. We observed growth inhibition of NMGB bacteria in the blood when we challenged mice immunized with Naid60-KLH followed by immunosuppression with live NMGB bacteria, supporting anti-NMGB Ab production in mice.…”

Section: Discussionmentioning

confidence: 70%

“…With respect to the capsular PS candidate, NMGB PS is an autoantigen that may elicit autoantibodies that bind both NMGB and neuronal tissue (13,14,31), because NMGB PS expresses a linear ␣(2-8) polymer of sialic acid; thus, NMGB PS has poor immunogenicity due to immune tolerance. The structural modification of capsular PS by the substitution of N-propionyl for N-acetyl groups proved to be highly immunogenic (15) but showed the possibility of eliciting autoantibodies (2,16,19). In a finestructure analysis of NMGB PS using MAbs, an immunogenic epitope was found which elicits antibodies that activate complement-mediated bacteriolysis and which has no autoantibody activity (16,42).…”

mentioning

confidence: 99%

Anti-Idiotypic Antibody as a Potential Candidate Vaccine forNeisseria meningitidisSerogroup B

et al. 2005

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Sepsis and meningitis caused by Neisseria meningitidis serogroup B (NMGB) are serious diseases in infants and young adults, but no effective vaccine is available. The capsular polysaccharide (PS) of NMGB has poor immunogenicity and a structural similarity to polysialic acid (PSA) on neuronal tissue that may elicit autoantibodies. Using HmenB3, a protective and nonautoreactive monoclonal antibody (MAb) to NMGB capsular PS, we produced an anti-idiotypic MAb, Naid60, which mimics the capsular PS of NMGB. We produced an anti-anti-idiotypic MAb, MoB34, by using the immunogenic site on Naid60 responsible for inducing the anti-NMGB PS antibody response. MoB34 elicited the complement-mediated killing of representative strains of serogroup B meningococci. MoB34 did not bind to CHP-134, a neuroblastoma cell line expressing ␣(2-8) PSA, or to mouse brain cryosections at a high concentration. Naid60-keyhole limpet hemocyanin immunization inhibited the growth of live NMGB in intraperitoneally challenged mice; in contrast, three of five control mice developed bacteremia. Thus, Naid60 has an immunogenic site that elicits antibodies with bactericidal activity against NMGB and no autoimmunity to PSA. We suggest that the immunogenic region of Naid60 is a candidate for the development of a new vaccine against NMGB.

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Protective efficacy of mouse serum to the N-propionyl derivative of meningococcal group B polysaccharide

Cited by 38 publications

References 11 publications

Activity and Cross-Reactivity of Antibodies Induced in Mice by Immunization with a Group B Meningococcal Conjugate

Activity and Cross-Reactivity of Antibodies Induced in Mice by Immunization with a Group B Meningococcal Conjugate

Rational chemical design of the carbohydrate in a glycoconjugate vaccine enhances IgM-to-IgG switching

Anti-Idiotypic Antibody as a Potential Candidate Vaccine forNeisseria meningitidisSerogroup B

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