Identification and Characterization of Stimulator of Interferon Genes As a Robust Adjuvant Target for Early Life Immunization

Frontiers in Immunology
Francesco BorrielloOfer Levy

Abstract

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 ~400-fold, an antibody subclass associated with the development of IFNγ-driven type 1 immunity in vivo and endowed with higher effector functions, by 42 days...Continue Reading

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Citations

Jan 7, 2020·Current Opinion in Pediatrics·Etsuro NanishiOfer Levy
Jun 5, 2018·AIDS Research and Human Retroviruses·Sallie PermarKristina De Paris
Apr 6, 2019·Frontiers in Immunology·Carolyn M Boudreau, Galit Alter
Jan 29, 2019·Frontiers in Immunology·Nikos E PapaioannouBarbara U Schraml
Jan 11, 2020·Frontiers in Immunology·Elena V VassilievaRichard W Compans
Jan 1, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Juan F Hernandez-FrancoHarm HogenEsch
Dec 2, 2020·Seminars in Immunology·Derek T O'HaganGiuseppe Lofano

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Methods Mentioned

BETA
flow cytometry
ELISA

Software Mentioned

SoftMax Pro
FlowJo

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