A5077076623- HIV Research and Treatment
- Virus-based gene therapy research
- Poxvirus research and outbreaks
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Immune Cell Function and Interaction
- COVID-19 Clinical Research Studies
- Circular RNAs in diseases
- Extracellular vesicles in disease
- T-cell and B-cell Immunology
- Research on Leishmaniasis Studies
- CAR-T cell therapy research
- Immune Response and Inflammation
- Advanced biosensing and bioanalysis techniques
- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- HIV/AIDS drug development and treatment
- interferon and immune responses
- Long-Term Effects of COVID-19
- SARS-CoV-2 detection and testing
- Mosquito-borne diseases and control
- Transgenic Plants and Applications
German Center for Infection Research
2020-2024
Ludwig-Maximilians-Universität München
2020-2024
Centro Nacional de Biotecnología
2012-2021
Consejo Superior de Investigaciones Científicas
2012-2019
The goal of successful anti-tumoural immunity is the development long-term protective to prevent relapse. Infiltration tumours with CD8+ T cells a resident memory (Trm) phenotype correlates improved survival. However, interplay circulating and Trm remains poorly explored in tumour immunity. Using different vaccination strategies that fine-tune generation or cells, here we show that, while both subsets are sufficient for anti-tumour immunity, presence improves efficacy. Transferred central...
Mammalian cells release different types of vesicles, collectively termed extracellular vesicles (EVs). EVs contain cellular microRNAs (miRNAs) with an apparent potential to deliver their miRNA cargo recipient affect the stability individual mRNAs and cells' transcriptome. The extent which miRNAs are exported via EV route whether they contribute cell-cell communication controversial. To address these issues, we defined multiple properties analyzed capacity packaged into target exert...
Resting CD4 T cells resist productive HIV-1 infection. The HIV-2/simian immunodeficiency virus protein viral accessory X (Vpx) renders these permissive to infection, presumably by alleviating blocks at cytoplasmic reverse transcription and subsequent nuclear import of reverse-transcription/pre-integration complexes (RTC/PICs). Here, spatial analyses using quantitative imaging techniques reveal that capsids containing RTC/PICs are readily imported into the nucleus, recruit host dependency...
ABSTRACT Mammalian cells release different types of vesicles, collectively termed extracellular vesicles (EVs). EVs contain cellular microRNAs (miRNAs) with an apparent potential to deliver their miRNA cargo recipient affect the stability individual mRNAs and cells’ transcriptome. The extent which miRNAs are exported via EV route whether they contribute cell-cell communication controversial. To address these issues, we analyzed capacity packaged into target exert biological functions. We...
Poxviruses use a complex strategy to escape immune control, by expressing immunomodulatory proteins that could limit their as vaccine vectors. To test the role of poxvirus NF-κB pathway inhibitors A52, B15, and K7 in immunity, we deleted genes an NYVAC (New York vaccinia virus) strain expresses HIV-1 clade C antigens. After infection mice, ablation A52R, B15R, K7R increased dendritic cell, natural killer neutrophil migration well chemokine/cytokine expression. Revertant viruses with these...
Abstract CD4 + T cells are central mediators of adaptive and innate immune responses constitute a major reservoir for human immunodeficiency virus (HIV) in vivo. Detailed investigations resting have been precluded by the absence efficient approaches genetic manipulation limiting our understanding HIV replication restricting efforts to find cure. Here we report method rapid, efficient, activation-neutral gene editing resting, polyclonal using optimized cell cultivation nucleofection...
ABSTRACT The generation of vaccines against HIV/AIDS able to induce long-lasting protective immunity remains a major goal in the HIV field. modest efficacy (31.2%) infection observed RV144 phase III clinical trial highlighted need for further improvement vaccine candidates, formulation, and regimen. In this study, we have generated two novel NYVAC vectors, expressing HIV-1 clade C gp140(ZM96) (NYVAC-gp140) or Gag(ZM96)-Pol-Nef(CN54) (NYVAC-Gag-Pol-Nef), defined their virological...
Heterologous vaccination based on priming with a plasmid DNA vector and boosting an attenuated vaccinia virus MVA recombinant, both vectors expressing the Leishmania infantum LACK antigen (DNA-LACK MVA-LACK), has shown efficacy conferring protection in murine canine models against cutaneus visceral leishmaniasis, but immune parameters of remain ill defined. Here we performed by flow cytometry depth analysis T cell populations induced BALB/c mice during protocol DNA-LACK/MVA-LACK, as well...
Neutrophils are antigen-transporting cells that generate vaccinia virus (VACV)-specific T-cell responses, yet how VACV modulates neutrophil recruitment and its significance in the immune response unknown. We generated an attenuated strain expresses HIV-1 clade C antigens but lacks three specific viral genes (A52R, K7R, B15R). found these act together to inhibit NFκB signaling pathway. Triple ablation modified restored function macrophages. After infection of mice, pathway activation led...
Abstract The emergence of more transmissible or aggressive variants SARS‐CoV‐2 requires the development antiviral medication that is quickly adjustable to evolving viral escape mutations. Here we report synthesis chemically stabilized small interfering RNA (siRNA) against SARS‐CoV‐2. siRNA can be further modified with receptor ligands such as peptides using Cu I ‐catalysed click‐chemistry. We demonstrate optimized siRNAs reduce loads and virus‐induced cytotoxicity by up five orders magnitude...
Here we describe the design and strength of a new synthetic late-early optimized (LEO) vaccinia virus (VACV) promoter used as transcriptional regulator GFP expression during modified Ankara infection. In contrast to described VACV (pS), LEO induced significantly higher levels in vitro within first hour after infection, which correlated with an enhancement GFP-specific CD8 T-cell response detected vivo, demonstrating its potential use future vaccines.
Despite the effectiveness of classic treatments and available diagnostic tools, cancer continues to be a leading world health problem, with devastating cancer-related death rates. Advances in oncolytic virotherapy have shown promise as potentially effective treatment options fight against cancer. The poxviruses many features that make them an attractive platform for development vectors, some candidates currently clinical trials. Here, we report design generation new vector based on vaccinia...
Vaccinia viruses (VACVs) with distinct early promoters have been developed to enhance antigen expression and improve antigen-specific CD8 T-cell responses. It has not demonstrated how the length of spacer between coding region gene its regulatory promoter motif influences expression, whether timing can modify CD4 response. We generated several recombinant VACVs based on attenuated modified vaccinia Ankara (MVA) strain, which express GFP or Leishmania LACK under control an optimized promoter,...
Replication-competent poxvirus vectors with an attenuation phenotype and a high immunogenic capacity of the foreign expressed antigen are being pursued as novel vaccine against different pathogens. In this investigation, we have examined replication characteristics two vaccinia virus (VACV) mutants, M65 M101. These mutants were generated after 65 101 serial passages persistently infected Friend erythroleukemia (FEL) cells. cultured cells origins, competent growth kinetics similar to or...
Immune cell phenotyping frequently detects lineage-unrelated receptors. Here, we report that surface receptors can be transferred from primary macrophages to CD4 T cells and identify the Fcγ receptor CD32 as driver cargo of this trogocytotic transfer. Filamentous CD32+ nanoprotrusions deposit distinct plasma membrane patches onto target cells. Transferred confer migration adhesion properties, macrophage-derived render resting susceptible infection by serving hotspots for HIV-1 binding....
Abstract Neutrophils are innate immune cells involved in the elimination of pathogens and can also induce adaptive responses. Nα Nβ neutrophils have been described with distinct vitro capacity to generate antigen-specific CD8 T-cell However, how these cell types exert their role vivo manipulation Nβ/Nα ratio influences vaccine-mediated responses not known. In this study, we find that neutrophil subtypes show migratory motility patterns different ability interact T spleen following vaccinia...
ABSTRACT Vaccines against the preerythrocytic stages of malaria are appealing because parasite can be eliminated before disease onset and they offer unique possibility targeting with both antibodies T cells. Although role CD8 + cells in is well documented, a highly effective cell-inducing vaccine remains to advanced. Here we report development prime-boost immunization regimen Plasmodium falciparum circumsporozoite protein (PfCS) fused oligomer-forming vaccinia virus A27 modified Ankara (MVA)...
Abstract Infection-neutralizing antibody responses after SARS-CoV-2 infection or COVID-19 vaccination are an essential part of antiviral immunity. This immune protection is challenged by the occurrence variants concern (VoCs) with escape properties, such as omicron (B.1.1.529) that rapidly spreading worldwide. Here, we report neutralizing dynamics in a longitudinal cohort convalescent and naïve individuals vaccinated mRNA BNT162b2 quantifying anti-SARS-CoV-2-spike antibodies determining...
There is an urgent need for the development of potent vaccination regimens that are able to induce specific T and B cell responses against human immunodeficiency virus type 1 (HIV-1) HIV-1. Here, we describe generation characterization a fusion antigen comprised HIV-1 envelope GP120 glycoprotein from clade C (GP120C) fused at its C-terminus, with modified vaccinia (VACV) 14K protein (A27L gene) (termed GP120C14K). The design directed towards improving immunogenicity GP120C through...
Background: Immunodominant CD8 T cell responses emerge in the first few weeks after HIV/SIV infection, suppress virus replication, and select for escape variants.Although T-cell based HIV vaccines have not successfully provided sterilizing immunity, vaccine-elicited cells may contribute to control of replication breakthrough viruses.It is critical that a vaccine generates an effective pool memory are available respond during acute infection effectively both chronic replication.Designing...
Abstract Die Entstehung von leichter übertragbaren oder aggressiveren Varianten SARS‐CoV‐2 erfordert die Entwicklung antiviralen Medikamenten, schnell an sich entwickelnde virale Escape ‐Mutationen anpassbar sind. Hier berichten wir über Synthese chemisch stabilisierter small interfering RNA (siRNA) gegen SARS‐CoV‐2. siRNA kann mit Hilfe Cu I ‐katalysierter Klick‐Chemie Rezeptorliganden wie Peptiden zusätzlich modifiziert werden. Wir zeigen, dass optimierte siRNAs Viruslast und...