Toward a New Kind of Vaccine: A Logical Extension of the Symmetrical Immune Network Theory

Gorczynski, Reg; Hoffmann, Geoffrey W.

doi:10.2196/ijmr.7612

Cited by 8 publications

(23 citation statements)

References 27 publications

(24 reference statements)

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“…Importantly, the antigen-specific regulation seen was independent of the specific antigens used to prepare the polyclonal immune Ig. One possible mechanism to help explain these effects involved the perturbation of regulatory T cell networks [19–21]. Such a concept is consistent with other data favouring a role for Tregs in control of allergic reactivity [22].…”

Section: Introductionsupporting

confidence: 74%

“…The protocol used to immunize naïve BALB/c mice to produce IgE against OVA was a modification of that described elsewhere [19]. 8 mice per group received 10 μg OVA emulsified in alum intraperitoneally (ip) in 0.2 ml PBS at days 0, day 14, 28 and 42 (see Fig.…”

Section: Methodsmentioning

confidence: 99%

“…A control group received no OVA immunization. In some cases, as documented in the text, groups of animals received weekly intramuscular (im) injections, beginning at day 7 post first OVA immunization, of 75 μg of pooled polyclonal anti-idiotype Ig [C3H anti–anti-C3H Ig (C3H anti-BL/6 absorbed with BL/6)] and 10 μg pooled polyclonal BL/6 anti-C3H immune Ig [19]. Other groups received 75 μg of human IMIG or 10 μg human anti-Tet Ig (both from GRIFOLS, Canada [23]).…”

Section: Methodsmentioning

confidence: 99%

“…Given this background it is evident that there remains an unmet need to develop novel therapies. We have recently reported on the use of a combined injection of polyclonal anti-idiotype antibodies, along with polyclonal immune antibodies, as a treatment aimed at “re-setting” immune regulatory networks in rodents [19]. This treatment led to a marked attenuation of a variety of immune reactivities, including decreased inflammatory cytokines and inflammatory colitis; suppression of skin graft rejection in a transplant model; and decreased IgE and IL-4 production as a marker of attenuation of allergen-induced Th2 activity in a rodent model (sensitization of mice to ovalbumin, OVA).…”

Section: Introductionmentioning

confidence: 99%

“…More recently we have extended these studies to show that attenuation of allergic responses (skin reactivity to peanut butter sensitization) can also be suppressed in Beagle dogs using the same methodological approach [23, 24]. Our hypothesis predicted that similar immunoregulation would be seen using treatment not just with immune Ig and anti-idiotype Ig from the same species (homologous), but across species (heterologous Ig treatment) [19–21, 23].…”

Section: Introductionmentioning

confidence: 99%

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Mechanism(s) of prolonged attenuation of allergic responses after modulation of idiotypic regulatory network

Gorczynski

Maqbool²,

Hoffmann³

2019

Allergy Asthma Clin Immunol

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BackgroundWe showed previously that allergic reactivity to ovalbumin (OVA) could be regulated in mice following perturbation of immune networks using combinations of an immune Ig along with anti-idiotypic Ig. We have explored features of this regulation including: its persistence after cessation of administration of combined Igs; the ability of heterologous Igs to produce immunoregulation; a role for Treg induction in regulation; and the ability to attenuate responses in mice pre-sensitized to an allergic stimulus.MethodsBALB/c mice were sensitized to OVA. Mice also received 5 weekly injections of immune Ig or anti-idiotype Ig (at separate sites) from either homologous (mouse) or heterologous (human) sources. In the latter case pooled IVIG (given IM, hence hereafter IMIG) was used as a source of anti-idiotype Ig, and human anti-Tet as immune Ig. Injections of the Ig were given from the time of OVA sensitization (to attenuate development of immunity), or after pre-sensitization of mice (to attenuate existing allergic responses). All mice were assayed for development of OVA-specific serum IgE and IgG, as well as the production of OVA-induced IL-2, IL-4, IL-13, IL-31 and IL-33 in splenocytes cultured for 72 h. In studies examining possible mechanism(s) responsible for inhibition of immunity mice received, in addition to the Ig treatments described, infusion of depleting anti-CD4, and/or anti-CD8 antibodies, or a mAb to TNFSFR25, known to expand Tregs implicated in regulation of Allo immunity.ResultsCombinations of both heterologous and homologous immune Igs and anti-idiotype Igs attenuated OVA allergic responses in both naïve and pre-sensitized mice. This attenuation persisted in mice greater than 14 weeks after cessation of treatment with the Igs used. Finally, depletion of either CD4 or CD8 cells ameliorated the suppressive effect seen, while the combination of anti-CD4 and anti-CD8 essentially abolished suppression. Suppression was further enhanced by anti-TNFSFR25 mAb.ConclusionsWe conclude that the combine Ig treatment protocols used produced a long-lasting suppression of allergic immunity, even in pre-sensitized animals. The effects seem to depend upon induction and expansion of Tregs and represents a novel approach to treatment of allergic disease in humans and other animals.

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Section: Introductionsupporting

confidence: 74%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%