CD4+ T cells enable the critical B cell humoral immune protection afforded by most effective vaccines. We and others have recently identified an alternative source of help for B cells in mice, invariant NK T (iNKT) cells. iNKT cells are innate glycolipid-specific T cells restricted to the nonpolymorphic Ag-presenting molecule CD1d. As such, iNKT cells respond to glycolipids equally well in all people, making them an appealing adjuvant for universal vaccines. We tested the potential for the iNKT glycolipid agonist, α-galactosylceramide (αGC), to serve as an adjuvant for a known human protective epitope by creating a nanoparticle that delivers αGC plus antigenic polysaccharides from Streptococcus pneumoniae. αGC-embedded nanoparticles activate murine iNKT cells and B cells in vitro and in vivo, facilitate significant dose sparing, and avoid iNKT anergy. Nanoparticles containing αGC plus S. pneumoniae polysaccharides elicits robust IgM and IgG in vivo and protect mice against lethal systemic S. pneumoniae. However, codelivery of αGC via nanoparticles actually eliminated Ab protection elicited by a T-independent S. pneumoniae vaccine. This is consistent with previous studies demonstrating iNKT cell help for B cells following acute activation, but negative regulation of B cells during chronic inflammation. αGC-containing nanoparticles represent a viable platform for broadly efficacious vaccines against deadly human pathogens, but their potential for eliminating B cells under certain conditions suggests further clarity on iNKT cell interactions with B cells is warranted.
BackgroundThe sensitivity of current antibody detection assays against Borrelia burgdorferi in the early stage of Lyme disease is very low. In children especially, who commonly have febrile viral illnesses, manifestations of early Lyme disease can be misdiagnosed. We previously demonstrated that IFNγ secretion could be detected in whole blood collected from Lyme disease patients at first clinical presentation following overnight incubation of the blood with peptides derived from B. burgdorferi. In the present study, we further evaluated the utility of IFNγ release for the laboratory diagnosis of Lyme disease in children with varying stages of the illness.MethodsChildren ages 2–18 years with no prior history of Lyme disease and with manifestations of Lyme disease at any stage were enrolled in the study. Sick and healthy controls were enrolled for comparison. We collected history and physical examination data and blood samples at the time of enrollment, at 1 month, and at 6 months. Standard 2-tier testing with ELISA (whole cell sonicate [WCS] and C6) and western blot were run in parallel to the IFNγ release assay for all blood samples. Sensitivity and specificity of the study assay were determined for presentation at all stages of Lyme disease. Clinical data were summarized.ResultsBlood samples from 22 patients with Lyme disease and 7 controls (4 sick, 3 healthy) were obtained at the first visit. The IFNγ release assay detected early and early disseminated Lyme disease with 78% sensitivity compared with 59% sensitivity of 2-tier testing in our study. For patients presenting with a single erythema migrans (EM) lesion, the IFNγ release assay detected Lyme disease with 63% sensitivity compared with 14% sensitivity with 2-tier testing. The IFNγ release assay had only 25% sensitivity for detecting late disease. A single control patient was positive for both the IFNγ release assay and 2-tier serology.ConclusionA novel IFNγ release assay demonstrated significantly increased sensitivity when compared with 2-tier testing in the laboratory diagnosis of Lyme disease in patients presenting with a single EM lesion. Future study is needed to determine its utility in detecting early Lyme disease in patients with nonspecific febrile illness in the absence of erythema migrans.Disclosures
R. Dattwyler, Qiagen: Collaborator, Research support. P. Arnaboldi, Qiagen: Collaborator, research materials.
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