A5045196734- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Hepatitis B Virus Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- Cancer Immunotherapy and Biomarkers
- COVID-19 Clinical Research Studies
- Cervical Cancer and HPV Research
- Malaria Research and Control
- Animal Virus Infections Studies
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- Neonatal Respiratory Health Research
- Helicobacter pylori-related gastroenterology studies
- Complement system in diseases
- Herpesvirus Infections and Treatments
- Influenza Virus Research Studies
- Tryptophan and brain disorders
- Carbohydrate Chemistry and Synthesis
- Digestive system and related health
- Cancer Cells and Metastasis
- Mosquito-borne diseases and control
- Glycosylation and Glycoproteins Research
- Long-Term Effects of COVID-19
University of Iowa
2020-2025
University Medical Center Groningen
2015-2020
University of Groningen
2016-2020
Radboud Institute for Molecular Life Sciences
2020
University Medical Center
2020
Radboud University Nijmegen
2020
Radboud University Medical Center
2020
Karolinska Institutet
2018
Royal Veterinary College
1996
Human papilloma virus (HPV)-induced cervical cancer constitutively expresses viral E6/E7 oncoproteins and is an excellent target for T cell-based immunotherapy. However, not all tumor-infiltrating cells confer equal benefit to patients, with epithelial being superior stromal cells.To assess whether the cell biomarker CD103 could specifically discriminate beneficial antitumor cells, association of clinicopathological variables outcome was analyzed in TCGA data set (n = 304) by...
A first-in-human phase I trial of Vvax001, an alphavirus-based therapeutic cancer vaccine against human papillomavirus (HPV)-induced cancers was performed assessing immunological activity, safety, and tolerability. Vvax001 consists replication-incompetent Semliki Forest virus replicon particles encoding HPV16-derived antigens E6 E7. Twelve participants with a history cervical intraepithelial neoplasia were included. Four cohorts three treated per dose level, ranging from 5 × 105 to 2.5 108...
Cancer immunotherapy urgently calls for methods to monitor immune responses at the site of cancer. Since activated T lymphocytes may serve as a hallmark anticancer responses, we targeted these cells using radiotracer N-(4-[18F]fluorobenzoyl)-interleukin-2 ([18F]FB-IL-2) positron emission tomography (PET) imaging. Thus, noninvasively monitored effects local tumor irradiation and/or immunization on tumor-infiltrating and systemic in tumor-bearing mice. A 10- 27-fold higher [18F]FB-IL-2 uptake...
Circulating memory CD8 T cell trafficking and protective capacity during liver-stage malaria infection remains undefined. We find that effector cells (Tem) infiltrate the liver within 6 hours after malarial or bacterial infections mediate pathogen clearance. Tem recruitment coincides with rapid transcriptional upregulation of inflammatory genes in Plasmodium-infected livers. Recruitment requires cell-intrinsic LFA-1 expression presence phagocytes. Rapid infiltration is distinct from to other...
Highlights•Tissue-resident memory (TRM) CD8+ T cells populate the brain•Brain TRM can be generated by peripheral viral infections•Repetitive stimulation shapes brain composition, location, and function•Repetitively stimulated protect against intracranial infectionSummaryThe human harbors virus-specific, tissue-resident cells. However, impact of repeated infection on generation, phenotype, localization, recall responses remains elusive. Here, utilizing two murine models infection, we...
Cervical cancer develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression early proteins E6 and E7. Our group pioneered recombinant viral vector system based on Semliki Forest virus (SFV) for vaccination against cervical cancer. The most striking benefit this alphavirus vector-based vaccine platform is its high potency. DNA vaccines the other hand, have major advantage respect to ease production. In study, benefits associated both SFV-based...
Radiation exposure occurs during medical procedures, nuclear accidents, or spaceflight, making effective countermeasures a public health priority. Naïve T cells are highly sensitive to radiation-induced depletion, although their numbers recover with time. Circulating memory CD8+ also depleted by radiation; however, do not recover. Critically, the impact of radiation on tissue-resident (TRM) remains unknown. Here, we found that sublethal thorax-targeted resulted in rapid and prolonged...
Protective lung tissue-resident memory CD8 + T cells (Trm) form after influenza A virus (IAV) infection. We show that IAV infection of mice generates CD69 CD103 and other cell populations in lung-draining mediastinal lymph nodes (mLNs) from circulating naive or cells. Repeated antigen exposure, mimicking seasonal infections, quaternary (4M) protect mLN viral better than 1M Better protection by 4M associates with enhanced granzyme A/B expression stable maintenance cells, vs the steady decline...
Abstract Production of IFN-γ by CD4 T cells is widely theorized to control Plasmodium parasite burden during blood-stage malaria. Surprisingly, the specific and crucial mechanisms through which this highly pleiotropic cytokine acts confer protection against malarial disease remain largely untested in vivo. Here we used a cell–restricted Cre-Lox excision mouse model test whether how cell–derived controls Although complete absence compromised acute chronic, recrudescent infections with P. c....
Sepsis reduces the number and function of memory CD8 T cells within host, contributing to long-lasting state immunoparalysis. Interestingly, relative susceptibility cell subsets quantitative/qualitative changes differ after cecal ligation puncture (CLP)–induced sepsis. Compared with circulatory (T<sub>CIRCM</sub>), moderate sepsis (0–10% mortality) does not result in numerical decline tissue-resident (T<sub>RM</sub>), which retain their "sensing alarm" IFN-γ–mediated effector function. To...
The skin is an attractive organ for immunization because of the presence antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity DNA vaccines in comparison to conventional methods. In this study, we explored efficacy tattoo injection a tumor based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo rSFV resulted antigen expression both and draining lymph nodes. with intramuscular...
Abstract Patients infected with SARS-CoV-2 experience variable disease susceptibility, and patients comorbidities such as sepsis are often hospitalized for COVID-19 complications. However, the extent to which initial infectious inoculum dose determines outcomes whether this can be used immunological priming in a genetically susceptible host has not been completely defined. We an established SARS-like murine model responses primary and/or secondary challenges hepatitis virus type 1 (MHV-1)...
Although tissue resident memory T cells (TRM) in the lung confer robust protection against secondary influenza infection, their vivo production of IFN-γ is unknown. In this study, using a mouse model, we evaluated by influenza-induced TRM (defined as CD103+) that localize to airways or parenchyma. Airway consist both CD11ahi and CD11alo populations, with low CD11a expression signifying prolonged airway residence. vitro, high-dose peptide stimulation evoked from most parenchymal TRM, whereas...
Abstract Tissue-resident memory T (T RM) cells are poised at mucosal sites to confer robust protection against secondary infection. In contrast skin and intestine, lung RMcells short lived with a decline in number coinciding protective immunity subsequent heterosubtypic influenza infections. Despite this causal relationship, the localization, dynamics function of Trm during responses remains poorly defined. To address this, we used two-photon intravital microscopy lungs assess real time...
Abstract Patients infected with SARS-CoV-2 can experience variable susceptibility and sepsis-like immune dysfunction. Also, patients comorbidities such as previous septic events are more likely to be hospitalized succumb COVID19 complications. However, the extent which respiratory beta-coronavirus pathology is dose dependent produces dysregulation in an experimental murine model not completely defined. We utilized established SARS-like by infecting Murine Hepatitis Virus 1 (MHV-1)...
Abstract Alveolar macrophages (AM) are one of the first immune cells to encounter pathogens in lung. However, role AMs early after infection remains be completely defined. To track virally infected cells, mice were with a panel fluorescent reporter-expressing respiratory viruses. By 6 hr post-infection (p.i.), AM numbers significantly declined. The remaining accounted for majority at time points, surpassing epithelium, but did not support significant viral replication. Strikingly,...