Bis-(3′,5′)-cyclic dimeric adenosine monophosphate: Strong Th1/Th2/Th17 promoting mucosal adjuvant

Ebensen, Thomas; Libanova, Rimma; Schulze, Kai; Yevsa, Tetyana; Morr, Michael; Guzmán, Carlos A.

doi:10.1016/j.vaccine.2011.05.026

Cited by 113 publications

(140 citation statements)

References 75 publications

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“…When administered intranasally with the S. pneumonia antigen pneumococcal surface protein A, cdGMP protected against S. pneumonia colonization (67). The ability of structurally related CDNs, such as cyclic di-inosine monophosphate and cyclic di-AMP, to adjuvant mucosal immunizations has also been reported (17,68). In contrast to the robust response to CDNs in mucosal immunization, the efficacy of CDNs as adjuvants in the setting of traditional parenteral immunization has been less clear, with much of the early published data focused on the use of CDNs to boost immunity against highly immunogenic model antigens and/or using large doses of CDNs.…”

Section: Type I Ifn and Tnf-α Play Complementary Roles Following Npcdmentioning

confidence: 94%

Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants

Hanson¹,

Crespo²,

Abraham³

et al. 2015

J. Clin. Invest.

311

294

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Section: Type I Ifn and Tnf-α Play Complementary Roles Following Npcdmentioning

confidence: 94%

Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants

Hanson¹,

Crespo²,

Abraham³

et al. 2015

J. Clin. Invest.

311

294

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“…Cyclic di-nucleotides that bind Stimulator of Interferon Gamma Genes (STING) were recently shown to be potential alternatives to cAMP-inducing bacterial toxins and derivatives as vaccine adjuvants. For example, STING ligands of bacterial origin, including 3′3′-cGAMP, c-di-AMP, and c-di-GMP, have been shown to effectively elicit mucosal and systemic immune responses following intranasal administration (64–66). More recently, targeting STING with 3′3′-cGAMP was found to be an effective strategy for enhancing the magnitude of immune responses and promoting IgA by sublingual immunization (67).…”

Section: Vaccine Adjuvants and Delivery Systems For Induction Of Mmentioning

confidence: 99%

Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems

Boyaka

2017

The Journal of Immunology

175

155

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Mucosal IgA or secretory IgA (SIgA) are structurally equipped to resist chemical degradation in the harsh environment of mucosal surfaces and the enzymes of host or microbial origin. Production of SIgA is finely regulated and distinct T-independent and T-dependent mechanisms orchestrate immunoglobulin heavy chain α class switching and SIgA responses against commensal and pathogenic microbes. Most infectious pathogens enter the host via mucosal surfaces. To provide a first line of protection at these entry ports, vaccines are being developed to induce pathogen-specific SIgA in addition to systemic immunity achieved by injected vaccines. Mucosal or epicutaneous delivery of vaccines helps target the inductive sites for IgA responses. The efficacy of such vaccines relies on the identification/engineering of vaccine adjuvants capable of supporting the development of SIgA alongside systemic immunity and delivery systems that improve vaccine delivery to the targeted anatomic sites and immune cells.

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“…Treatment with CDNs stimulates innate immune cells to control Klebsiella pneumoniae and Staphylococcus aureus infection in vivo (Karaolis et al, 2007a, 2007b). Additionally, immunizing with model antigens in conjunction with CDNs results in distinct immune responses depending on the route of delivery, with subcutaneous administration leading to a Th1/Th2 response and mucosal administration leading to a Th17 response (Ebensen et al, 2011). CDNs have also been shown to elicit protective antibody-based immunity when used as a vaccine adjuvant against the extracellular bacterial pathogens S. aureus and Streptococcus pneumoniae (Ebensen et al, 2007a, 2007b; Ogunniyi et al, 2008; Hu et al, 2009; Yan et al, 2009; Libanova et al, 2010; Madhun et al, 2011; Dubensky et.…”

Section: Introductionmentioning

confidence: 99%

STING-Activating Adjuvants Elicit a Th17 Immune Response and Protect against Mycobacterium tuberculosis Infection

et al. 2018

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SUMMARY There are a limited number of adjuvants that elicit effective cell-based immunity required for protection against intracellular bacterial pathogens. Here, we report that STING-activating cyclic dinucleotides (CDNs) formulated in a protein subunit vaccine elicit long-lasting protective immunity to Mycobacterium tuberculosis in the mouse model. Subcutaneous administration of this vaccine provides equivalent protection to that of the live attenuated vaccine strain Bacille Calmette-Guérin (BCG). Protection is STING dependent but type I IFN independent and correlates with an increased frequency of a recently described subset of CXCR3-expressing T cells that localize to the lung parenchyma. Intranasal delivery results in superior protection compared with BCG, significantly boosts BCG-based immunity, and elicits both Th1 and Th17 immune responses, the latter of which correlates with enhanced protection. Thus, a CDN-adjuvanted protein subunit vaccine has the capability of eliciting a multi-faceted immune response that results in protection from infection by an intracellular pathogen.

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Bis-(3′,5′)-cyclic dimeric adenosine monophosphate: Strong Th1/Th2/Th17 promoting mucosal adjuvant

Cited by 113 publications

References 75 publications

Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants

Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants

Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems

STING-Activating Adjuvants Elicit a Th17 Immune Response and Protect against Mycobacterium tuberculosis Infection

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