We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
IL-28B is a Key Regulator of B- and T-Cell Vaccine Responses against Influenza.
- Authors
Egli, Adrian; Santer, Deanna M.; O'Shea, Daire; Barakat, Khaled; Syedbasha, Mohammedyaseen; Vollmer, Madeleine; Baluch, Aliyah; Bhat, Rakesh; Groenendyk, Jody; Joyce, Michael A.; Lisboa, Luiz F.; Thomas, Brad S.; Battegay, Manuel; Khanna, Nina; Mueller, Thomas; Tyrrell, D. Lorne J.; Houghton, Michael; Humar, Atul; Kumar, Deepali
- Abstract
Influenza is a major cause of morbidity and mortality in immunosuppressed persons, and vaccination often confers insufficient protection. IL-28B, a member of the interferon (IFN)-λ family, has variable expression due to single nucleotide polymorphisms (SNPs). While type-I IFNs are well known to modulate adaptive immunity, the impact of IL-28B on B- and T-cell vaccine responses is unclear. Here we demonstrate that the presence of the IL-28B TG/GG genotype (rs8099917, minor-allele) was associated with increased seroconversion following influenza vaccination (OR 1.99 p = 0.038). Also, influenza A (H1N1)-stimulated T- and B-cells from minor-allele carriers showed increased IL-4 production (4-fold) and HLA-DR expression, respectively. In vitro, recombinant IL-28B increased Th1-cytokines (e.g. IFN-γ), and suppressed Th2-cytokines (e.g. IL-4, IL-5, and IL-13), H1N1-stimulated B-cell proliferation (reduced 70%), and IgG-production (reduced>70%). Since IL-28B inhibited B-cell responses, we designed antagonistic peptides to block the IL-28 receptor α-subunit (IL28RA). In vitro, these peptides significantly suppressed binding of IFN-λs to IL28RA, increased H1N1-stimulated B-cell activation and IgG-production in samples from healthy volunteers (2-fold) and from transplant patients previously unresponsive to vaccination (1.4-fold). Together, these findings identify IL-28B as a key regulator of the Th1/Th2 balance during influenza vaccination. Blockade of IL28RA offers a novel strategy to augment vaccine responses.
- Subjects
REGULATOR genes; B cells; T cells; VACCINES; SINGLE nucleotide polymorphisms
- Publication
PLoS Pathogens, 2014, Vol 10, Issue 12, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1004556