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Identification and Characterization of Stimulator of Interferon Genes As a Robust Adjuvant Target for Early Life Immunization
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Borriello, F. (author)
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Pietrasanta, C. (author)
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- Lai, Jacqueline, 1980 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Walsh, L. M. (author)
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Sharma, P. (author)
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O'Driscoll, D. N. (author)
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Ramirez, J. (author)
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Brightman, S. (author)
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Pugni, L. (author)
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Mosca, F. (author)
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Burkhart, D. J. (author)
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Dowling, D. J. (author)
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Levy, O. (author)
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(creator_code:org_t)
- 2017-12-12
- 2017
- English.
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
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Abstract
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- Immunization is key to preventing infectious diseases, a leading cause of death early in life. However, due to age-specific immunity, vaccines often demonstrate reduced efficacy in newborns and young infants as compared to adults. Here, we combined in vitro and in vivo approaches to identify adjuvant candidates for early life immunization. We employed newborn and adult bone marrow-derived dendritic cells (BMDCs) to perform a screening of pattern recognition receptor agonists and found that the stimulator of interferon genes ligand 2' 3'-cGAMP (hereafter cGAMP) induces a comparable expression of surface maturation markers in newborn and adult BMDCs. Then, we utilized the trivalent recombinant hemagglutinin (rHA) influenza vaccine, Flublok, as a model antigen to investigate the role of cGAMP in adult and early life immunization. cGAMP adjuvantation alone could increase rHA-specific antibody titers in adult but not newborn mice. Remarkably, as compared to alum or cGAMP alone, immunization with cGAMP formulated with alum (Alhydrogel) enhanced newborn rHA-specific IgG2a/ c titers similar to 400-fold, an antibody subclass associated with the development of IFN gamma-driven type 1 immunity in vivo and endowed with higher effector functions, by 42 days of life. Highlighting the amenability for successful vaccine formulation and delivery, we next confirmed that cGAMP adsorbs onto alum in vitro. Accordingly, immunization early in life with (cGAMP(+) alum) promoted IFN. production by CD4(+) T cells and increased the proportions and absolute numbers of CD4(+) CXCR5(+) PD-1(+) T follicular helper and germinal center (GC) GL-7(+) CD138(+) B cells, suggesting an enhancement of the GC reaction. Adjuvantation effects were apparently specific for IgG2a/c isotype switching without effect on antibody affinity maturation, as there was no effect on rHA-specific IgG avidity. Overall, our studies suggest that cGAMP when formulated with alum may represent an effective adjuvantation system to foster humoral and cellular aspects of type 1 immunity for early life immunization.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- vaccines
- adjuvants
- newborn
- antigen-presenting cells
- germinal centers
- T follicular helper cells
- c-di-gmp
- neonatal dendritic cells
- regulatory b-cells
- mouse
- bone-marrow
- vaccine adjuvants
- mucosal adjuvant
- sting pathway
- innate
- immunity
- i interferons
- helper-cells
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Borriello, F.
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Pietrasanta, C.
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Lai, Jacqueline, ...
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Walsh, L. M.
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Sharma, P.
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O'Driscoll, D. N ...
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show more...
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Ramirez, J.
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Brightman, S.
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Pugni, L.
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Mosca, F.
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Burkhart, D. J.
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Dowling, D. J.
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Levy, O.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Frontiers in Imm ...
- By the university
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University of Gothenburg