Diagnosing Zika virus infection against a background of other flaviviruses: Studies in high resolution serological analysis
| Autor: | Hansen, Sören, Hotop, Sven-Kevin, Faye, Oumar, Ndiaye, Oumar, Böhlken-Fascher, Susanne, Pessôa, Rodrigo, Hufert, Frank, Stahl-Hennig, Christiane, Frank, Ronald, Czerny, Claus-Peter, Schmidt-Chanasit, Jonas, Sanabani, Sabri S, Sall, Amadou A, Niedrig, Matthias, Brönstrup, Mark, Fritz, Hans-Joachim, Abd El Wahed, Ahmed |
|---|---|
| Přispěvatelé: | HZI, Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig Germany. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Protein Array Analysis
lcsh:Medicine chemical and pharmacologic phenomena Cross Reactions Antibodies Viral Article Disease Outbreaks Diagnosis Differential Species Specificity Diagnosis Cabo Verde Humans ddc:610 lcsh:Science Antigens Viral Zika Virus Infection Flavivirus lcsh:R Zika Virus Senegal Zika virus infection flaviviruses Viral infection lcsh:Q Peptides 610 Medizin und Gesundheit Brazil |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) Scientific Reports Scientific reports |
| Popis: | BACKGROUND: Antibody-mediated targeting of regulatory T cell receptors such as CTLA-4 enhances antitumor immune responses against several cancer entities including malignant melanoma. Yet, therapeutic success in patients remains variable underscoring the need for novel combinatorial approaches. METHODS: Here we established a vaccination strategy that combines engagement of the nucleic acid-sensing pattern recognition receptor RIG-I, antigen and CTLA-4 blockade. We used in vitro transcribed 5'-triphosphorylated RNA (3pRNA) to therapeutically target the RIG-I pathway. We performed in vitro functional analysis in bone-marrow derived dendritic cells and investigated RIG-I-enhanced vaccines in different murine melanoma models. FINDINGS: We found that protein vaccination together with RIG-I ligation via 3pRNA strongly synergizes with CTLA-4 blockade to induce expansion and activation of antigen-specific CD8+ T cells that translates into potent antitumor immunity. RIG-I-induced cross-priming of cytotoxic T cells as well as antitumor immunity were dependent on the host adapter protein MAVS and type I interferon (IFN-I) signaling and were mediated by dendritic cells. INTERPRETATION: Overall, our data demonstrate the potency of a novel combinatorial vaccination strategy combining RIG-I-driven immunization with CTLA-4 blockade to prevent and treat experimental melanoma. FUND: German Research Foundation (SFB 1335, SFB 1371), EMBO, Else Kröner-Fresenius-Foundation, German Cancer Aid, European Hematology Association, DKMS Foundation for Giving Life, Dres. Carl Maximilian and Carl Manfred Bayer-Foundation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|