IL-28B is a Key Regulator of B- and T-Cell Vaccine Responses against Influenza

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Infection with influenza viruses is associated with high morbidity and mortality. Therefore, vaccination is recommended in immunosuppressed patients, however often the post-vaccine induced protection is insufficient. Factors associated with reduced vaccine responses may guide preventive strategies and could offer novel targets for adjuvants. Here, we explore the impact of IL-28B on B- and T-cell responses during vaccination. We found that a single nucleotide polymorphism (minor allele genotype) in the IL-28B gene was associated with a significant increase in the antibody seroconversion rate following influenza vaccination. Interestingly, this SNP reduces the expression of IL-28B. In addition, in vitro stimulation of peripheral blood mononuclear cells from patients with the SNPs had increased IL-4 production in CD4 T-cells. As a potential mechanism, we show that recombinant IL-28B inhibits influenza stimulated Th2 cytokine release, B-cell activation/proliferation and H1N1-induced IgG secretion. Next, we developed antagonistic peptides to block the IFN-λ receptor. Pre-treatment with the antagonistic peptides increased in vitro B-cell activation and antibody production in healthy individuals and transplant recipients. Together, these findings identify IL-28B as a key regulator of Th1/Th2 balance during influenza vaccination. Blockade of the IFN-λ receptor with antagonistic peptides may offer a novel strategy to augment vaccine responses.

Vyšlo v časopise: IL-28B is a Key Regulator of B- and T-Cell Vaccine Responses against Influenza. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004556
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004556

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