Optimized conjugation ratios lead to allergen immunostimulatory oligodeoxynucleotide conjugates with retained immunogenicity and minimal anaphylactogenicity

Horner, Anthony A.; Takabayashi, Kenji; Beck, Lucinda; Sharma, Bhavya B.; Zubeldía, J M; Baird, Stephen M.; Tuck, Stephan; Libet, Lev; Spiegelberg, Hans L.; Liu, Fu‐Tong; Raz, Eyal

doi:10.1067/mai.2002.126660

Cited by 48 publications

(46 citation statements)

References 29 publications

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“…Previous investigations have demonstrated that AIC is significantly more immunogenic than allergen alone or allergen mixed with ISS (11,(22)(23)(24)(25). Therefore, in parallel with studies of i.n.…”

Section: Intranasal Aic It Is More Effective Than Id Aic It For Thementioning

confidence: 93%

“…The ISS and M-ODN selected for study have previously been shown to have high and low immunostimulatory activity, respectively (22). To produce OVA conjugated to ISS (OVA:ISS) and to M-ODN (OVA: M-ODN), maleimido groups were introduced onto exposed lysines of the OVA molecule by incubation with a 20 M excess of sulfosuccinimidyl 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (Pierce Chemicals, Rockford, IL) for 2 h, followed by purification on a NAP-25 column (Amersham Pharmacia, Uppsala, Sweden).…”

Section: Reagentsmentioning

confidence: 99%

“…IT with a simple protein allergen. Immunostimulatory sequence oligodeoxynucleotide (ISS) has proven to be a powerful vaccine adjuvant for the prevention and reversal of allergic hypersensitivities (21), and allergen ISS conjugates (AICs; allergens physically linked to ISS) are particularly promising IT reagents, because they have proven to be more immunogenic than allergen mixed with ISS and are less allergenic in models of IgE-dependent hypersensitivity (11,(22)(23)(24)(25). Therefore, we also evaluated the potential of i.n.…”

mentioning

confidence: 99%

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Intranasal Immunotherapy Is More Effective Than Intradermal Immunotherapy for the Induction of Airway Allergen Tolerance in Th2-Sensitized Mice

Takabayashi¹,

Libet²,

Chisholm³

et al. 2003

The Journal of Immunology

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Immunotherapy (IT) by injection more readily induces clinical tolerance to stinging insects than to respiratory allergens. However, while systemic immunization induces adaptive responses systemically, the induction of mucosal immunity generally requires local Ag exposure. Taken together, these observations suggest that the poor success rate of systemic IT for asthma could be a consequence of inadequate immune modulation in the airways. In support of this position, investigations presented in this report demonstrate that allergen IT more effectively induces airway allergen tolerance in Th2-sensitized mice, when delivered by the intranasal (i.n.) vs the intradermal (i.d.) route. Moreover, compared with native allergen, allergen immunostimulatory sequence oligodeoxynucleotide conjugate proved to be a more effective i.n. IT reagent for protecting allergic mice from airway hypersensitivity responses. Furthermore, for both native allergen and allergen immunostimulatory sequence oligodeoxynucleotide conjugate, i.n. and i.d. IT delivery were similarly effective in modulating systemic immune profiles in Th2-sensitized mice, while only i.n. IT had significant immunomodulatory activity on B and T cell responses in the airways. The present investigations may be the first to suggest that i.n. IT is more effective than i.d. IT for the treatment of asthma. Furthermore, our results suggest that modulating airway rather than systemic immunity may be the more important therapeutic target for the induction of clinical tolerance to respiratory allergens.

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Section: Intranasal Aic It Is More Effective Than Id Aic It For Thementioning

confidence: 93%

Section: Reagentsmentioning

confidence: 99%

mentioning

confidence: 99%

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Intranasal Immunotherapy Is More Effective Than Intradermal Immunotherapy for the Induction of Airway Allergen Tolerance in Th2-Sensitized Mice

Takabayashi¹,

Libet²,

Chisholm³

et al. 2003

The Journal of Immunology

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“…Afterwards, the presence of these molecules in the environment potentates the differentiation of naïve Th0 cells into Th1 and cytotoxic T lymphocytes [19]. Thus, the deviation exerted in the immune response could be taken in advantageous to coadminister antigens as well as CpG sequences, leading to a potent antigen-specific Th1 type response and being a promising strategy for a wide range of diseases, such as bacterial infections [20], cancer [21,22] and allergy [23].…”

Section: Introductionmentioning

confidence: 99%

Co-encapsulation of an antigen and CpG oligonucleotides into PLGA microparticles by TROMS technology

Román

Irache

Gómez

et al. 2008

European Journal of Pharmaceutics and Biopharmaceutics

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“…Synthetic oligodeoxynucleotides containing CpG motifs (CpG-ODN) derived from bacterial DNA promoted Th1-like cytokine production and decreased the spontaneous synthesis of IgE Abs in allergic individuals in vitro (17)(18)(19)(20). This immunomodulatory capacity was even more pronounced when CpG-ODN were chemically linked to a single defined allergen (21)(22)(23). Both conjugated CpG-ODN and monophosphoryl lipid A have been successfully applied in clinical trials and revealed promising results regarding the treatment of type I allergies (24 -26).…”

mentioning

confidence: 99%

A Novel Approach to Specific Allergy Treatment: The Recombinant Allergen-S-Layer Fusion Protein rSbsC-Bet v 1 Matures Dendritic Cells That Prime Th0/Th1 and IL-10-Producing Regulatory T Cells

Gerstmayr

Ilk

Schabussova

et al. 2007

The Journal of Immunology

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An ideal vaccine for allergen-specific immunotherapy of type I allergies should display reduced mediator-releasing capacity, induce maturation of APC, and modify the disease-eliciting Th2-dominated allergen-specific response to a more physiological response. We have previously shown that rSbsC-Bet v 1, the recombinant fusion protein of a bacterial surface (S-layer) protein of Geobacillus stearothermophilus ATCC 12980 and the major birch pollen allergen Bet v 1, exhibited reduced allergenicity and induced IFN-γ and IL-10 synthesis in Bet v 1-specific Th2 clones. In this study, we characterized the effects of rSbsC-Bet v 1 on immature monocyte-derived dendritic cells (mdDC) and the consequences for the polarization of naive CD4+ T lymphocytes isolated from the blood of birch pollen-allergic patients. mdDC responded to rSbsC-Bet v 1 with a significant up-regulation of costimulatory molecules, functional maturation, and the synthesis of IL-10 and IL-12. mdDC matured with rSbsC-Bet v 1 induced the differentiation of naive T cells into IFN-γ-producing cells. This effect was IL-12 dependent. In parallel, a substantial number of naive T cells developed into IL-10-producing CD25+Foxp3+CLTA-4+ cells capable of active suppression. Thus, rSbsC-Bet v 1 showed immune stimulatory capacity on DC, which then promoted the simultaneous differentiation of Th0/Th1 cells and regulatory T cells. These data further support that the concept of conjugating allergens to bacterial agents is a promising approach to improve vaccines for specific immunotherapy of atopic allergies.

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Optimized conjugation ratios lead to allergen immunostimulatory oligodeoxynucleotide conjugates with retained immunogenicity and minimal anaphylactogenicity

Cited by 48 publications

References 29 publications

Intranasal Immunotherapy Is More Effective Than Intradermal Immunotherapy for the Induction of Airway Allergen Tolerance in Th2-Sensitized Mice

Intranasal Immunotherapy Is More Effective Than Intradermal Immunotherapy for the Induction of Airway Allergen Tolerance in Th2-Sensitized Mice

Co-encapsulation of an antigen and CpG oligonucleotides into PLGA microparticles by TROMS technology

A Novel Approach to Specific Allergy Treatment: The Recombinant Allergen-S-Layer Fusion Protein rSbsC-Bet v 1 Matures Dendritic Cells That Prime Th0/Th1 and IL-10-Producing Regulatory T Cells

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