A5041735439- Immune Cell Function and Interaction
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Immune Response and Inflammation
- Virus-based gene therapy research
- Animal Virus Infections Studies
- RNA Interference and Gene Delivery
- Influenza Virus Research Studies
- Fusion materials and technologies
- Microstructure and Mechanical Properties of Steels
- Magnetic confinement fusion research
- Intermetallics and Advanced Alloy Properties
- Shape Memory Alloy Transformations
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- Cytomegalovirus and herpesvirus research
- Viral Infectious Diseases and Gene Expression in Insects
- Landslides and related hazards
- Animal Disease Management and Epidemiology
- HIV/AIDS drug development and treatment
- Hepatitis B Virus Studies
- Respiratory viral infections research
Osaka University
2016-2025
National Institute of Biomedical Innovation, Health and Nutrition
2016-2025
Kyoto University
2019-2025
University of California, Santa Barbara
2004-2025
RIKEN Center for Advanced Intelligence Project
2024-2025
Hamamatsu University School of Medicine
2023-2024
Immune Regulation (United Kingdom)
2024
Osaka International Cancer Institute
2022-2024
National Institutes of Health
2007-2022
National Institute of Allergy and Infectious Diseases
2012-2022
CD4 T follicular helper (TFH) cells interact with and stimulate the generation of antigen-specific B cells. TFH cell interaction correlates production SIV-specific immunoglobulins. However, fate their participation in SIV-induced antibody is not well understood. We investigated phenotype, function, location, molecular signature rhesus macaques. Similar to human counterparts, macaques represented a heterogeneous population respect cytokine function. In highly differentiated subpopulation...
CD8+ T cell exhaustion represents a major hallmark of chronic HIV infection. Two key transcription factors governing differentiation, T-bet and Eomesodermin (Eomes), have previously been shown in mice to differentially regulate part through direct modulation PD-1. Here, we examined the relationship between these expression several inhibitory receptors (PD-1, CD160, 2B4), functional characteristics memory differentiation cells treated The PD-1, 2B4 on total was elevated chronically infected...
The interaction between follicular T helper cells (TFH) and B in the lymph nodes spleen has a major impact on development of antigen-specific cell responses during infection or vaccination. Recent studies described functional equivalent these among circulating CD4 cells, referred to as peripheral TFH cells. Here, we characterize phenotype vitro activity populations, well effect HIV populations. In co-culture experiments confirmed CXCR5+ from HIV-uninfected donors provide help more...
T follicular helper cells associate with development of highly mutated neutralizing antibodies against SHIV.
Pathogen recognition receptor (PRR) agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity efficacy of vaccines. Using an original vitro approach prime naive precursors from unfractionated human peripheral blood mononuclear cells, we assessed influence cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), a ligand for stimulator interferon genes (STING), on induction antigen-specific CD8+ T cells. We found that...
Continuing emergence of variants concern resulting in reduced SARS-CoV-2 vaccine efficacy necessitates additional prevention strategies. The structure VLPCOV-01, a lipid nanoparticle-encapsulated, self-amplifying RNA COVID-19 with comparable immune response to BNT162b2, was revised by incorporating modified base, 5-methylcytosine, reduce reactogenicity, and an updated receptor-binding domain derived from the Brazil (gamma) variant. Interim analyses phase 1 dose-escalation booster vaccination...
In response to viral infection, the innate immune system recognizes nucleic acids and then induces production of proinflammatory cytokines type I interferons (IFNs). Toll-like receptor 7 (TLR7) TLR9 detect RNA DNA, respectively, in endosomal compartments, leading activation nuclear factor kappaB (NF-kappaB) IFN regulatory factors (IRFs) plasmacytoid dendritic cells. During such TLR signaling, TNF receptor-associated 6 (TRAF6) is essential for NF-kappaB IFN. contrast, RIG-like helicases...
Abstract Developing predictive animal models to assess how candidate vaccines and infection influence the ontogenies of Envelope (Env)-specific antibodies is critical for development an HIV vaccine. Here we use two nonhuman primate compare roles antigen persistence, diversity innate immunity. We perform longitudinal analyses Env-specific B-cell receptor responses SHIV AD8 Env protein vaccination with eight different adjuvants. A subset -infected animals higher viral loads greater show...
VLPCOV-01 is a lipid nanoparticle-encapsulated self-amplifying RNA (saRNA) vaccine that expresses membrane-anchored receptor-binding domain (RBD) derived from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. A phase 1 study of conducted (jRCT2051210164). Participants who completed two doses BNT162b2 mRNA previously are randomized to receive one intramuscular vaccination 0.3, 1.0, or 3.0 μg VLPCOV-01, 30 BNT162b2, placebo. No serious adverse events have been...
Abstract Several vaccines have been widely used to counteract the global pandemic caused by SARS-CoV-2. However, due rapid emergence of SARS-CoV-2 variants concern (VOCs), further development that confer broad and longer-lasting protection against emerging VOCs are needed. Here, we report immunological characteristics a self-amplifying RNA (saRNA) vaccine expressing Spike (S) receptor binding domain (RBD), which is membrane-anchored fusing with an N-terminal signal sequence C-terminal...
Monocytes/macrophages are major targets of human immunodeficiency virus type 1 (HIV-1) infection. The viral preintegration complex (PIC) HIV-1 enters the nuclei monocyte-derived macrophages, but very little PIC migrates into immature monocytes. Vpr, one accessory gene products HIV-1, is essential for nuclear import in these cells, although role Vpr entry mechanism remains to be clarified. We have shown previously that targeted envelope and then transported nucleus by importin alpha alone, an...
Abstract Background The differentiation of CD8 + T lymphocytes following priming naïve cells is central in the establishment adaptive immune response. Yet, molecular events underlying this process are not fully understood. MicroRNAs have been recently shown to play a key role regulation haematopoiesis mouse, but their implication peripheral lymphocyte humans remains largely unknown. Methods In order explore potential microRNAs cell humans, microRNA expression profiles were analysed using...
Abstract DNA vaccines are attractive immunogens for priming humoral and cellular immune responses to the encoded Ag. However, their ability induce Ag-specific CD8+ T cell requires improvement. Among strategies improving vaccine immunogenicity booster vaccinations, alternate formulations, electroporation, genetic adjuvants, but few, such as extracellular vesicles (EVs), target natural Ag delivery systems. By focusing on CD63, a tetraspanin protein expressed various membranes, including EVs,...
Follicular helper T (Tfh) cells within secondary lymphoid organs control multiple steps of B cell maturation and antibody (Ab) production. HIV-1 infection is associated with an altered differentiation Tfh isolated from lymph nodes HIV-infected (HIV+) individuals provide inadequate help in vitro. However, the mechanisms underlying this impairment function are not fully defined. Using a unique collection splenocytes, we compared frequency, phenotype transcriptome subsets spleens HIV negative...
Recent advances have made modeling human small intestines in vitro possible, but it remains a challenge to recapitulate fully their structural and functional characteristics. We suspected interstitial flow within the intestine, powered by circulating blood plasma during embryonic organogenesis, be vital factor. aimed construct an vivo-like multilayered intestinal tissue incorporating into system and, turn, developed micro-small intestine differentiating definitive endoderm mesoderm cells...
Recombinant adenovirus (rAd) vectors are being investigated as vaccine delivery vehicles in preclinical and clinical studies. rAds constructed from different serotypes differ receptor usage, tropism, ability to activate cells, aspects of which likely contribute their immunogenicity profiles. In this study, we compared the infectivity cell stimulatory capacity recombinant serotype 5 (rAd5), 28 (rAd28), 35 (rAd35) association with respective We found that rAd28 rAd35 infected led vitro...
The maintenance of effective immunity over time is dependent on the capacity hematopoietic stem cells (HSCs) to sustain pool immunocompetent mature cells. Decline immune competence with old age may from HSC defects, including reduced self-renewal potential and impaired lymphopoiesis, as suggested in murine models. To obtain further insights into aging-related alteration hematopoiesis, we performed a comprehensive study blood progenitor (HPCs) older humans. In elderly, HPCs present active...
Cancer‑associated fibroblasts (CAFs) are implicated in the strong malignancy of pancreatic cancer (PC). Various CAF subtypes have different functions, and their heterogeneity likely influence PC. Meanwhile, it is known that senescent cells can create a tumor‑promoting microenvironment by inducing senescence‑associated secretory phenotype (SASP). In present study, effects individual differences CAFs on PC were investigated with focus cellular senescence. First, primary cultures from 8...
The emergence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variants necessitated a rapid evaluation system for their pathogenesis. Lung epithelial cells are entry points; however, in addition to limited source, the culture human alveolar is especially complicated. Induced pluripotent stem (iPSCs) an alternative source primary cells. Here, we report model distinguishing SARS-CoV-2 at high resolution, using separately induced iPSC-derived and airway micro-patterned plates....
Dendritic cells (DCs) are essential antigen-presenting for the induction of T cell immunity against HIV. On other hand, due to susceptibility DCs HIV infection, virus replication is strongly enhanced in DC-T interaction via an immunological synapse formed during antigen presentation process. When HIV-1 isolated from individuals newly infected with mixture R5 and X4 variants, predominant, irrespective route infection. Because early massive occurs activated such T-cell activation induced by...
Biofilms play a pivotal role in medical device-related infections. However, epidemiological analysis of biofilm formation and genotyping among clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients with orthopaedic infections has rarely been reported. A total 168 MRSA strains were examined: 23 infection (the device group); 55 device-non-related nondevice 90 asymptomatic nasal carriers colonization group). Pulsed-field gel electrophoresis five methods including agr...