In Vivo Synthesis of Cyclic-di-GMP Using a Recombinant Adenovirus Preferentially Improves Adaptive Immune Responses against Extracellular Antigens

The Journal of Immunology : Official Journal of the American Association of Immunologists
Fadel S AlyaqoubAndrea Amalfitano

Abstract

There is a compelling need for more effective vaccine adjuvants to augment induction of Ag-specific adaptive immune responses. Recent reports suggested the bacterial second messenger bis-(3'-5')-cyclic-dimeric-guanosine monophosphate (c-di-GMP) acts as an innate immune system modulator. We recently incorporated a Vibrio cholerae diguanylate cyclase into an adenovirus vaccine, fostering production of c-di-GMP as well as proinflammatory responses in mice. In this study, we recombined a more potent diguanylate cyclase gene, VCA0848, into a nonreplicating adenovirus serotype 5 (AdVCA0848) that produces elevated amounts of c-di-GMP when expressed in mammalian cells in vivo. This novel platform further improved induction of type I IFN-β and activation of innate and adaptive immune cells early after administration into mice as compared with control vectors. Coadministration of the extracellular protein OVA and the AdVCA0848 adjuvant significantly improved OVA-specific T cell responses as detected by IFN-γ and IL-2 ELISPOT, while also improving OVA-specific humoral B cell adaptive responses. In addition, we found that coadministration of AdVCA0848 with another adenovirus serotype 5 vector expressing the HIV-1-derived Gag Ag or the Clos...Continue Reading

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Citations

Jun 25, 2016·Chemical Communications : Chem Comm·Clement Opoku-TemengHerman O Sintim
Dec 11, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Estefania Rodriguez-GarciaMirja Hommel
Mar 8, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sze-Wah TseEric Huang

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