Monoclonal Antibody-Mediated Modulation of the Humoral Immune Response against Mucosally Applied<i>Streptococcus mutans</i>

Brady, L. Jeannine; Tilburg, M. L. J. A. Van; Alford, C.E.; McArthur, William P.

doi:10.1128/iai.68.4.1796-1805.2000

Cited by 27 publications

(62 citation statements)

References 86 publications

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“…We have identified an immunomodulatory monoclonal antibody (MAb) that recognizes the P1 surface adhesin of Streptococcus mutans. The immunogenicity of mucosally applied S. mutans in BALB/c mice is altered when MAb 6-11A is complexed with P1 on the cell surface (8).…”

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confidence: 99%

“…Immunomodulatory effects of 6-11A vary depending on the route of mucosal immunization and on the coating concentration of the antibody (8). Binding of MAb 6-11A to S. mutans prior to immunization of mice by gastric intubation influences the isotype distribution of the anti-P1 serum IgG response and the specificity of serum IgG antibodies against large polypeptide fragments of P1 generated by partial digestion with N-chlorosuccinimide (NCS).…”

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Further Characterization of Immunomodulation by a Monoclonal Antibody againstStreptococcus mutansAntigen P1

et al. 2004

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We demonstrated previously that mucosal immunization of mice with Streptococcus mutans coated with the monoclonal antibody (MAb) 6-11A directed against the major surface adhesin protein P1 results in changes in the amount, isotype distribution, and specificity of serum antibodies compared with animals immunized with bacteria only. We now show that the specificity of the mucosal secretory IgA response was also influenced by this MAb. Changes in antibody specificity were associated with changes in biological activity. Serum samples which differed in antibody reactivity with P1 polypeptides generated by partial digestion with N-chlorosuccinimide but not in isotype distribution or overall reactivity with S. mutans or intact P1 demonstrated a statistically significant difference in the ability to inhibit bacterial adherence to salivary-agglutinin-coated hydroxyapatite beads. Serum IgG antibodies against P1 from mice immunized with either S. mutans alone or S. mutans coated with 6-11A were shown to recognize antigenic determinants dependent on the presence of the central proline-rich repeat domain, a segment necessary for the structural integrity of the molecule. However, no statistically significant differences were observed in antibody reactivity with a panel of six partial P1 polypeptides encoded by overlapping spaP subclones, suggesting that the targets of biologically relevant antibodies involve complex epitopes not reconstituted by the recombinant products tested. Lastly, we show that binding of MAb 6-11A to P1 on the surface of S. mutans alters P1's susceptibility to proteolytic digestion. Hence, changes in antigen processing and presentation may contribute to the immunomodulatory effects of this MAb.

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Further Characterization of Immunomodulation by a Monoclonal Antibody againstStreptococcus mutansAntigen P1

et al. 2004

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“…In addition, however, antibodies in ICs can also exert epitopespecific effects and modulate the specificity of the antibodies induced. Mechanisms such as epitope shielding or antibodymediated conformational changes have been proposed to explain the phenomena observed (28,38,44,45).…”

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“…We have therefore conducted a model immunization study in mice and investigated the outcome of antibody responses to the TBE virus E protein in complex with monoclonal antibodies (MAbs) specific for each of the three domains of E. Potentially, the presence of preexisting antigen-specific antibodies and the formation of ICs can have a variety of indirect, non-antigen-specific effects, primarily mediated by the interaction of the Fc parts with Fc receptors that are present on innate and adaptive immune cells (reviewed in references 36 and 37). Such interactions may lead to an enhancement or a decrease of the overall antibody responses, depending on the specific situation of infection or immunization, the nature of the antigen, and the characteristics of the antibodies in the ICs (27,29,(38)(39)(40)(41). The potential beneficial nature of such general antibody-mediated effects may be a means for designing more-effective immunization protocols, e.g., to overcome impaired germinal center responses in the elderly (42), or for developing therapeutic vaccines (43).…”

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Immunization with Immune Complexes Modulates the Fine Specificity of Antibody Responses to a Flavivirus Antigen

Tsouchnikas

Zlatkovic

Jarmer

et al. 2015

J Virol

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The antibody response to proteins may be modulated by the presence of preexisting antigen-specific antibodies and the formation of immune complexes (ICs). Effects such as a general increase or decrease of the response as well as epitope-specific phenomena have been described. In this study, we investigated influences of IC immunization on the fine specificity of antibody responses in a structurally well-defined system, using the envelope (E) protein of tick-borne encephalitis (TBE) virus as an immunogen. TBE virus occurs in Europe and Asia and-together with the yellow fever, dengue, West Nile, and Japanese encephalitis viruses-represents one of the major human-pathogenic flaviviruses. Mice were immunized with a dimeric soluble form of E (sE) alone or in complex with monoclonal antibodies specific for each of the three domains of E, and the antibody response induced by these ICs was compared to that seen after immunization with sE alone. Immunoassays using recombinant domains and domain combinations of TBE virus sE as well as the distantly related West Nile virus sE allowed the dissection and quantification of antibody subsets present in postimmunization sera, thus generating fine-specificity patterns of the polyclonal responses. There were substantially different responses with two of the ICs, and the differences could be mechanistically related to (i) epitope shielding and (ii) antibody-mediated structural changes leading to dissociation of the sE dimer. The phenomena described may also be relevant for polyclonal responses upon secondary infections and/or booster immunizations and may affect antibody responses in an individual-specific way. IMPORTANCEInfections with flaviviruses such as yellow fever, dengue, Japanese encephalitis, West Nile, and tick-borne encephalitis (TBE) viruses pose substantial public health problems in different parts of the world. Antibodies to viral envelope protein E induced by natural infection or vaccination were shown to confer protection from disease. Such antibodies can target different epitopes in E protein, and the fine specificities of polyclonal responses can differ between individuals. We conducted a mouse immunization study with TBE E protein alone or complexed to monoclonal antibodies specific for each of the three protein domains. We demonstrated that phenomena such as epitope shielding and antibody-induced structural changes can profoundly influence the fine specificity of antibody responses to the same immunogen. The study thus provided important new information on the potential immunomodulatory role of preexisting antibodies in a flavivirus system that can be relevant for understanding individual-specific factors influencing antibody responses in sequential flavivirus infections and/or immunizations. Several mosquito-and tick-transmitted flaviviruses are important human pathogens and have a substantial public health impact in countries of endemicity (1). These include the yellow fever (YF), dengue (DEN), West Nile (WN), Japanese encephalitis (JE), and tick-borne...

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“…The immunoregulatory properties of antibody have been recognized since the earliest passive immunization experiments, and the potential to modulate an immune response by deliberate immunization with antigen bound by antibody has been demonstrated in numerous instances over the decades (Brady et al, 2000;Alber et al, 2001;Antoniou and Watts, 2002;Rafiq et al, 2002). The ability of P. niruri to influence humoral response will confer protection to animals or man.…”

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confidence: 99%

Immunomodulatory activities of methanol extract of the whole aerial part of Phyllantus niruri L.

Eze¹,

Nworu²,

Esimone³

et al. 2014

J. Pharmacognosy Phytother.

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In this study, the effect of methanol extract of whole aerial parts of Phyllantus niruri on some specific and non-specific immune response was investigated. The effects of P. niruri on in vivo leucocyte mobilization, delayed type hypersensitivity (DTHR) response, and humoral antibody (HA) response were determined in rats. Acute toxicity profile of P. niruri was evaluated in mice. The Agar induced in vivo leucocytes mobilization into the rats peritoneal fluid was (P<0.05) increased by P. niruri N (200 and 400 mg/kg) in a dose related manner. The total leucocytes count was higher in the extract treated group than the control group. Polymorphonuclear neutrophils (PMNS) were more mobilized than the lymphocytes. P. niruri at 100, 200 and 400 mg/kg body weight produced significant (P<0.05) inhibition of DTH response in rat by 30.55, 66.67 and 44.44%, respectively with 200 mg/kg being most significant. The primary and secondary sheep red blood cell antibody titres were significantly elevated when compared with the control group. P. niruri administered orally showed no death or signs of acute intoxication at doses up to 5000 mg/kg after 24 h of observation. The result of this study showed that the methanol extract of P. niruri whole plant possess immunomodulatory activities and warrant further investigation to determine the specific constituent(s) of the plant responsible for this property.

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Monoclonal Antibody-Mediated Modulation of the Humoral Immune Response against Mucosally AppliedStreptococcus mutans

Cited by 27 publications

References 86 publications

Further Characterization of Immunomodulation by a Monoclonal Antibody againstStreptococcus mutansAntigen P1

Further Characterization of Immunomodulation by a Monoclonal Antibody againstStreptococcus mutansAntigen P1

Immunization with Immune Complexes Modulates the Fine Specificity of Antibody Responses to a Flavivirus Antigen

Immunomodulatory activities of methanol extract of the whole aerial part of Phyllantus niruri L.

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