کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5536562 | 1402295 | 2017 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Dynamics of APC recruitment at the site of injection following injection of vaccine adjuvants
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کلمات کلیدی
MPLSite of injectionTDBDDADLNTDMCFSEPam3CSK4CFAHPGAPCPAMhpiSOILPSInnate immunity - ایمنی ذاتیinterleukin - اینترلوکینtumor necrosis factor alpha - تومور نکروز عامل آلفاVaccine adjuvant - داروی واکسنdimethyldioctadecylammonium bromide - دی متیل دیکتوسیدیل آمونیوم برومیدDendritic cell - سلول دندریتیکantigen presenting cell - سلولهای پردازنده آنتیژنIntramuscular - عضلانیTNF-α - فاکتور نکروز توموری آلفاlipopolysaccharide - لیپوپلی ساکاریدMonophosphoryl lipid A - لیپید مونوفسفریل Ai.m. - من هستم.Mechanism of action - مکانیسم عملcontralateral - کنتراستDraining lymph node - گره لنفاوی تخلیه
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Vaccines often contain adjuvants to strengthen the response to the vaccine antigen. However, their modes of action at the site of injection (SOI) are poorly understood. Therefore, we assessed the local effects of adjuvant on the innate immune system in mice. We investigated the safe, widely used adjuvants MF59 and aluminum hydroxide (alum), as well as trehalose-6,6â²-dibehenate (TDB), Complete Freund's Adjuvant (CFA) and the Toll-Like-Receptor-ligands lipopolysaccharide (LPS) and Pam3CysSerLys4 (Pam3CSK4). We assessed muscle immune cell infiltration after adjuvant injection and observed 16Â h post immunization (hpi) an increased influx with CFA, MF59 and TDB, but not with alum, LPS or Pam3CSK4. An elevated influx with the latter three became visible only 72Â hpi. Contribution of granulocytes, macrophages and dendritic cells to the influx differed per adjuvant and in time. Adjuvants generally induced a local pro-inflammatory micro-milieu that was transient except for CFA and TDB. The gene expression of CXCL-1, CCL-2 and CCL-5, involved in recruitment of immune cells, varied per adjuvant and corresponded grossly with the observed influx of granulocytes and monocytes/macrophages. Muscles injected with CFA or MF59 (when co-injected with peptide) resulted in APC ex vivo capable to induce proliferation of peptide-specific T-cells. By adding in vitro an excess of peptide to the APC/T cell co-cultures, we observed an adjuvant-enhanced co-stimulation or antigen presentation by APC after CFA- but not MF59-injection. After TDB-injection this effect was observed only at 72Â hpi, but not 24Â hpi. Thus the cellular influx profile and the local cytokine and chemokine micro-milieu in the muscle were strongly influenced by the type of adjuvant. Additionally, the capacity of muscle APC to load and present antigen was affected by the adjuvant. These findings may assist the development of novel adjuvanted vaccines in a more rational manner.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Vaccine - Volume 35, Issue 12, 14 March 2017, Pages 1622-1629
Journal: Vaccine - Volume 35, Issue 12, 14 March 2017, Pages 1622-1629
نویسندگان
Susan van Aalst, Irene Stephanie Ludwig, Peter Johannes Sylvester van Kooten, Ruurd van der Zee, Willem van Eden, Femke Broere,