The STING activator c-di-AMP exerts superior adjuvant properties than the formulation poly(I:C)/CpG after subcutaneous vaccination with soluble protein antigen or DEC-205-mediated antigen targeting to dendritic cells.

Abstract

Vaccination is the most efficient strategy to protect from infectious diseases and the induction of a protective immune response not only depends on the nature of the antigen, but is also influenced by the vaccination strategy and the co-administration of adjuvants. Therefore, the precise monitoring of adjuvant candidates and their immune modulatory properties is a crucial step in vaccine development. Here, one central aspect is the induction of appropriate humoral and cellular effector mechanisms. In our study we performed a direct comparison of two promising candidates in adjuvant development, the STING activator bis-(3,5)-cyclic dimeric adenosine monophosphate (c-di-AMP) and the Toll-like receptor ligand formulation poly(I:C)/CpG. These were evaluated in C57BL/6 mice using the model antigen ovalbumin (OVA) in subcutaneous vaccination with soluble protein as well as in a dendritic cell (DC) targeting approach (αDEC-OVA). Strikingly, c-di-AMP as compared to poly(I:C)/CpG resulted in significantly higher antigen-specific IgG antibody levels when used in immunization with soluble OVA as well as in antigen targeting to DC. In vaccination with soluble OVA, c-di-AMP induced a significantly stronger CTL, Th1 and IFNγ-producing CD8+ memory T cell response than poly(I:C)/CpG. The response was CTL and Th1 cell dominated, a profile shared by both adjuvants. In the context of targeting OVA to DC, c-di-AMP induced significantly increased Th1 and Th2 cell responses as compared to poly(I:C)/CpG. Interestingly, the Th1 response dominated the overall T cell response only when c-di-AMP was used, indicating a distinct modulatory property of c-di-AMP when the DC targeting immunization approach was exploited. Taken together, we describe superior properties of c-di-AMP as compared to poly(I:C)/CpG in subcutaneous vaccination with soluble antigen as well as antigen targeting to DC. This indicates exceptionally effective adjuvant properties for c-di-AMP and provides compelling evidence of its potential for further adjuvant development, especially also when using DC targeting approaches.

• Authors: Julia Volckmar, Laura Knop, Sabine Stegemann-Koniszewski, Kai Schulze, Thomas Ebensen, Carlos A Guzmán, Dunja Bruder
• Journal: Vaccine (Vaccine) Vol. 37 Issue 35 Pg. 4963-4974 (08 14 2019) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 31320219 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Antigens, CD
• Cancer Vaccines
• DEC-205 receptor
• Dinucleoside Phosphates
• Immunoglobulin G
• Lectins, C-Type
• Minor Histocompatibility Antigens
• Oligodeoxyribonucleotides
• Receptors, Cell Surface
• cyclic diadenosine phosphate
• Ovalbumin
• Poly I-C

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Antigens, CD (immunology)
• Cancer Vaccines
• Dendritic Cells (immunology)
• Dinucleoside Phosphates (administration & dosage, immunology)
• Female
• Immunoglobulin G (immunology)
• Injections, Subcutaneous
• Lectins, C-Type (immunology)
• Mice
• Mice, Inbred C57BL
• Minor Histocompatibility Antigens (immunology)
• Oligodeoxyribonucleotides (administration & dosage, immunology)
• Ovalbumin (administration & dosage, immunology)
• Poly I-C (administration & dosage, immunology)
• Receptors, Cell Surface (immunology)
• Specific Pathogen-Free Organisms
• Vaccination