Chapter 22 : Bis-(3′,5′)-Cyclic Di-GMP: Promising Adjuvant for Vaccine Design

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Vaccines represent the most cost-efficient intervention against infections, and their therapeutic use against infections, cancer, and chronic inflammatory diseases raised considerable interest. Traditional vaccines were based on the use of killed or attenuated microorganisms or relatively crude antigenic extracts. Adjuvants can exert their biological activity through different mechanisms, such as (i) affecting the intrinsic properties of a given antigen, (ii) creating a depot which results in slow antigen release, and (iii) direct targeting and activation of key components of the innate immune system. Thus, adjuvants not only promote the induction of strong immune responses, thereby reducing the amount of antigen needed (i.e., antigen sparing), but also enable us to fine-tune the elicited responses through their immune modulatory properties. In this regard, it would be particularly appealing to identify nonprotein compounds exhibiting activity as mucosal adjuvants, which are poorly immunogenic and amenable for incorporation in different vaccine formulations. Immunization with model antigens coadministered with cyclic di-GMP (c-di-GMP) by the i.n. route resulted in a significantly improved stimulation of antigen-specific immune responses at both the systemic and mucosal levels in comparison to mice immunized by the parenteral route. In the particular case of c-di-GMP, pretreatment or coadministration to animals receiving a bacterial challenge resulted in enhanced clearance.

Citation: Ebensen T, Libanova R, Guzmán C. 2010. Bis-(3′,5′)-Cyclic Di-GMP: Promising Adjuvant for Vaccine Design, p 311-319. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch22
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Figure 1.

Vaccination with an antigen stimulates the innate and adaptive immune responses which afford humoral and cellular immunity.

Citation: Ebensen T, Libanova R, Guzmán C. 2010. Bis-(3′,5′)-Cyclic Di-GMP: Promising Adjuvant for Vaccine Design, p 311-319. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch22
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Image of Figure 2.
Figure 2.

Coadministration of c-di-GMP as a parenteral or mucosal adjuvant with model- or disease-related antigens resulted in efficient humoral and cellular immune responses in the host.

Citation: Ebensen T, Libanova R, Guzmán C. 2010. Bis-(3′,5′)-Cyclic Di-GMP: Promising Adjuvant for Vaccine Design, p 311-319. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch22
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Image of Figure 3.
Figure 3.

Coadministration of c-di-GMP stimulates a broad spectrum of antigen-specific immune responses irrespective of the administration route (8, 9, 18). Animals were immunized with phosphate-buffered saline alone (control), model antigens alone, such as ovalbumin (OVA) or β-galactosidase (β-Gal), or antigen coadministered with c-di-GMP on days 0, 14, and 28. Mice showed strong antigen-specific humoral and cellular immune responses in comparison to mice vaccinated with the antigen alone.

Citation: Ebensen T, Libanova R, Guzmán C. 2010. Bis-(3′,5′)-Cyclic Di-GMP: Promising Adjuvant for Vaccine Design, p 311-319. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch22
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