Journal
FRONTIERS IN IMMUNOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2017.01772
Keywords
vaccines; adjuvants; newborn; antigen-presenting cells; germinal centers; T follicular helper cells; antibodies; stimulator of interferon genes
Categories
Funding
- U.S. National Institutes of Health (NIH) [1R01AI100135-01, 3R01AI067353-05S1]
- National Institutes of Allergy and Infectious Diseases (NIAID), NIH
- Department of Health and Human Services, NIH [1U01AI124284-01, HHSN272201400052C]
- Global Health award from the Bill & Melinda Gates Foundation [OPPGH5284]
- Grand Challenges Explorations award from the Bill & Melinda Gates Foundation [OPP1035192]
- internal Boston Children's Hospital award
- UniNA
- Compagnia di San Paolo
- scholarship J. Miglierina, Fondazione Comunitaria del Varesotto, Varese, Italy
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available