Immunostimulatory DNA Is a Potent Mucosal Adjuvant

Horner, Anthony A.; Ronaghy, Arash; Cheng, Pei-Ming; Nguyen, Minh-Duc; Cho, Hearn J.; Broide, David H.; Raz, Eyal

doi:10.1006/cimm.1998.1400

Cited by 94 publications

(60 citation statements)

References 17 publications

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“…In particular, ISS-ODN induces the secretion of Th1-type cytokines and upregulates the expression of costimulatory molecules on antigenpresenting cells (6). These immunostimulatory characteristics of ISS-ODN have been utilized to elicit Th1-dependent immune responses (7) and mucosal immunity (8), leading to an enhanced host defense against invading pathogens (9).…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptor 9–induced type I IFN protects mice from experimental colitis

Katakura¹,

Lee²,

et al. 2005

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Experimental colitis is mediated by inflammatory or dysregulated immune responses to microbial factors of the gastrointestinal tract. In this study we observed that administration of Toll-like receptor 9 (TLR9) agonists suppressed the severity of experimental colitis in RAG1 -/-but not in SCID mice. This differential responsiveness between phenotypically similar but genetically distinct animals was related to a partial blockade in TLR9 signaling and defective production of type I IFN (i.e., IFN-α/β) in SCID mice upon TLR9 stimulation. The addition of neutralization antibodies against type I IFN abolished the antiinflammatory effects induced by TLR9 agonists, whereas the administration of recombinant IFN-β mimicked the antiinflammatory effects induced by TLR9 agonists in this model. Furthermore, mice deficient in the IFN-α/β receptor exhibited more severe colitis than wild-type mice did upon induction of experimental colitis. These results indicate that TLR9-triggered type I IFN has antiinflammatory functions in colitis. They also underscore the important protective role of type I IFN in intestinal homeostasis and suggest that strategies to modulate innate immunity may be of therapeutic value for the treatment of intestinal inflammatory conditions.

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Section: Introductionmentioning

confidence: 99%

Toll-like receptor 9–induced type I IFN protects mice from experimental colitis

Katakura¹,

Lee²,

et al. 2005

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“…Although most vaccines using CpG ODN as adjuvant have been administered parenterally, there have been several reports concerning the enhancement of mucosal immune responses following i.n. delivery (23)(24)(25)(26). However, no studies have compared the ability of CpG and non-CpG ODN to induce mucosal immune responses in the genital tract and protection from IVAG virus challenge.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, several studies showed that intranasal (i.n.) delivery of CpG ODN as an adjuvant results in strong systemic and mucosal immune responses to coadministered Ags including hepatitis B surface Ag (23,24), ␤-galactosidase (25), and whole killed influenza virus (26). Although non-CpG ODN had an adjuvant effect at mucosal surfaces, this was weaker than with CpG ODN and was not Th1-biased (27).…”

mentioning

confidence: 99%

Intranasal Immunization with CpG Oligodeoxynucleotides as an Adjuvant Dramatically Increases IgA and Protection Against Herpes Simplex Virus-2 in the Genital Tract

Gallichan¹,

Woolstencroft²,

Guarasci

et al. 2001

The Journal of Immunology

200

134

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Development of vaccines capable of preventing the transmission or limiting the severity of sexually transmitted viruses, such as HSV and HIV, will likely be dependent on the induction of potent long-lasting mucosal immune responses in the genital tract. Recently, synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs were shown to serve as potent adjuvants for the induction of mucosal immune responses. Here, we show that intranasal immunization with CpG ODN, plus recombinant glycoprotein B (rgB) of HSV-1, results in significantly elevated levels of specific anti-gB IgA Abs in vaginal washes that remained high throughout the estrous cycle. Additionally, dramatically elevated numbers of specific IgA Ab-secreting cells were present and persisted in the genital tract in response to intravaginal (IVAG) HSV-2 challenge. HSV-2-specific CTL were observed at moderate levels in the spleens of CpG or non-CpG ODN-immunized mice. In contrast, strong CTL responses were observed locally in the genital tissues of both groups following IVAG HSV-2 challenge. Interestingly, mice immunized intranasally with rgB plus CpG ODN, but not non-CpG ODN, were significantly protected following IVAG HSV-2 challenge. Measurement of virus in protected CpG-immunized mice revealed a log lower level of replication within the first few days after infection. In conclusion, these results indicate that intranasal immunization with CpG ODN plus protein mediates immunity in the female genital tract capable of protecting against a sexually transmitted pathogen.

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“…Horner et al [90] demonstrated in mice that CpG given intranasally together with ß-galactosidase was as good as CT for induction of antigen-specific mucosal IgA responses (Th2-responses), whereas a systemic Th1-response was obtained. Several other studies using other antigens confirmed the adjuvant effect following intranasal administration leading to a Th1-biased immune response, but did not always demonstrate the strong IgA response seen by Horner et al [137].…”

Section: Tlr9-bindingmentioning

confidence: 99%

Adjuvants modulating mucosal immune responses or directing systemic responses towards the mucosa

et al. 2006

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-In developing veterinary mucosal vaccines and vaccination strategies, mucosal adjuvants are one of the key players for inducing protective immune responses. Most of the mucosal adjuvants seem to exert their effect via binding to a receptor/or target cells and these properties were used to classify the mucosal adjuvants reviewed in the present paper: (1) ganglioside receptor-binding toxins (cholera toxin, LT enterotoxin, their B subunits and mutants); (2) surface immunoglobulin binding complex CTA1-DD; (3) TLR4 binding lipopolysaccharide; (4) TLR2-binding muramyl dipeptide; (5) Mannose receptor-binding mannan; (6) Dectin-1-binding ß 1,3/1,6 glucans; (7) TLR9-binding CpG-oligodeoxynucleotides; (8) Cytokines and chemokines; (9) Antigen-presenting cell targeting ISCOMATRIX and ISCOM. In addition, attention is given to two adjuvants able to prime the mucosal immune system following a systemic immunization, namely 1α, 25(OH) 2 D 3 and cholera toxin.

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Immunostimulatory DNA Is a Potent Mucosal Adjuvant

Cited by 94 publications

References 17 publications

Toll-like receptor 9–induced type I IFN protects mice from experimental colitis

Toll-like receptor 9–induced type I IFN protects mice from experimental colitis

Intranasal Immunization with CpG Oligodeoxynucleotides as an Adjuvant Dramatically Increases IgA and Protection Against Herpes Simplex Virus-2 in the Genital Tract

Adjuvants modulating mucosal immune responses or directing systemic responses towards the mucosa

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