Dual Immunoregulatory Effects of Monoclonal IgG‐Antibodies: Suppression and Enhancement of the Antibody Response

Wiersma, Erik J.; Coulie, Pierre G.; Heyman, Birgitta

doi:10.1111/j.1365-3083.1989.tb01143.x

Cited by 66 publications

(59 citation statements)

References 31 publications

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“…As stated above, orally immunized mice which received S. mutans saturated with MAb 6-11A demonstrated lower total levels of anti-S. mutans and anti-P1 serum IgG than animals which received bacteria alone or bacteria coated with a 0.1ϫ saturating concentration of MAb. Binding of different MAbs to a vaccine antigen prior to parenteral immunization has been reported to exert both suppressive and enhancing effects on the magnitude of the elicited response (5,69,80). In this instance, much of the decrease in anti-P1 serum IgG reactivity could be accounted for by a decrease in reactivity against the A region as measured by ELISA.…”

Section: Discussionmentioning

confidence: 81%

“…Binding of different monoclonal antibodies (MAbs) to a vaccine antigen prior to parenteral immunization has been reported to exert a variety of immunomodulatory effects, including suppression, enhancement, and differences in the specificity of the elicited response (4,5,6,69,80). Protection against colonization with any microorganism would be expected to depend on induction of antibodies of the correct specificity and isotype.…”

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confidence: 99%

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

et al. 2000

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Systemic immunization with antigen coupled to monoclonal antibody (MAb) has been used by several investigators to increase the number of MAb-producing hybridomas against an antigen and to elicit antibodies specific for poorly immunogenic epitopes. This strategy has implications for vaccine design in that protective immunity is not necessarily directed at immunodominant epitopes of pathogens and may be improved by deliberately shifting the immune response toward subdominant epitopes. To our knowledge, no studies to date have addressed the potential for immunomodulatory activity mediated by MAbs bound to mucosally applied antigen. To test whether administration of an exogenous MAb directed against a streptococcal surface protein could influence the humoral immune response, BALB/c mice were immunized orally by gastric intubation or intranasally with Streptococcus mutans alone or S. mutans complexed with a MAb directed against the major surface protein P1. Significant changes in the subclass distribution, as well as the specificity, of anti-P1 serum immunoglobulin G antibodies were demonstrated in groups of mice which received S. mutans coated with the anti-P1 MAb versus those which received S. mutans alone. Alterations in the humoral immune response were dependent on the amount of anti-P1 MAb used to coat the bacteria. In addition, differences in the anti-P1 immune responses were observed between groups of mice immunized via oral versus intranasal routes. In summary, an exogenous MAb complexed with a streptococcal antigen prior to mucosal immunization can influence the immunoglobulin isotype and specificity of the host humoral immune response against the antigen.

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Section: Discussionmentioning

confidence: 81%

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confidence: 99%

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

et al. 2000

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“…We conclude that the IgE-mediated enhancement is mediated exclusively via CD23 and not via any other IgE receptor. To investigate whether our CD23-deficient mice were able to produce Abs in other situations, they were immunized with IgG/BSA-TNP complexes also known to enhance Ab responses in vivo (34,38). CD23-deficient mice were indeed capable of mounting an Ab response to IgG/BSA-TNP and even showed a higher response than wild-type controls (Fig.…”

Section: Impaired Ige-mediated Enhancement Of Ab Responses In Cd23-dementioning

confidence: 99%

Restoration of the Antibody Response to IgE/Antigen Complexes in CD23-Deficient Mice by CD23+ Spleen or Bone Marrow Cells

Gustavsson

Wernersson

Heyman

2000

The Journal of Immunology

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Mice immunized with IgE/Ag complexes produce significantly more Ag-specific Abs than mice immunized with Ag alone. The enhancement is mediated via the low-affinity receptor for IgE (FcεRII or CD23), as shown by its complete absence in mice pretreated with mAbs specific for CD23 and in CD23-deficient mice. Because the constitutive expression of murine CD23 is limited to B cells and follicular dendritic cells (FDCs), one of these cell types is likely to be involved. One of the suggested modes of action of IgE/CD23 is to increase the ability of B cells to present Ag to T cells, as demonstrated to take place in vitro. Another possibility is that FDCs capture the IgE/Ag complexes and present these directly to B cells. The purpose of the present study was to determine whether CD23+ B cells or FDCs are responsible for the IgE/CD23-mediated enhancement of specific Ab responses in vivo. We show that the enhancement is completely restored in irradiated CD23-deficient mice reconstituted with CD23+ spleen or bone marrow cells. In these mice, the B cells are CD23+ and the FDCs are presumably CD23− because the FDCs are radiation resistant and are reported not to be replaced by donor cells after this type of cell transfer. In contrast, enhancement was not restored in irradiated wild-type mice reconstituted with CD23− cells. These results indicate that CD23+ B cells, and not FDCs, are the cells that capture IgE/Ag complexes and induce enhancement of Ab responses in vivo.

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“…They promote Fc receptor-mediated recognition by antigen-presenting cells (3,28). Immune complexes also activate the complement cascade (14,32). It has also been suggested that through binding to FcR and complement receptors, there is localization of the complex on follicular dendritic cells (DCs) which carry both types of receptor or that the complexes might directly stimulate B cells via their complement receptors (10).…”

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Highly Immunogenic and Protective Recombinant Vaccine Candidate Expressed in Transgenic Plants

et al. 2005

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Vaccine development has been hampered by difficulties in developing new and safe adjuvants, so alternative technologies that offer new avenues forward are urgently needed. The goal of this study was to express a monoclonal recombinant immune complex in a transgenic plant. A recombinant protein consisting of a tetanus toxin C fragment-specific monoclonal antibody fused with the tetanus toxin C fragment was designed and expressed. Immune complex formation occurred between individual fusion proteins to form immune complexlike aggregates that bound C1q and Fc␥RIIa receptor and could be targeted to antigen-presenting cells. Unlike antigen alone, the recombinant immune fusion complexes were highly immunogenic in mice and did not require coadministration of an adjuvant (when injected subcutaneously). Indeed, these complexes elicited antibody titers that were more than 10,000 times higher than those observed in animals immunized with the antigen alone. Furthermore, animals immunized with only 1 g of recombinant immune complex without adjuvant were fully protected against lethal challenge. This the first report on the use of a genetic fusion between antigen and antibody to ensure an optimal expression ratio between the two moieties and to obtain fully functional recombinant immune complexes as a new vaccine model.

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Dual Immunoregulatory Effects of Monoclonal IgG‐Antibodies: Suppression and Enhancement of the Antibody Response

Cited by 66 publications

References 31 publications

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

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

Restoration of the Antibody Response to IgE/Antigen Complexes in CD23-Deficient Mice by CD23+ Spleen or Bone Marrow Cells

Highly Immunogenic and Protective Recombinant Vaccine Candidate Expressed in Transgenic Plants

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