A5049896667- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- HIV/AIDS Research and Interventions
- Immunotherapy and Immune Responses
- HIV/AIDS drug development and treatment
- Cytomegalovirus and herpesvirus research
- Hepatitis B Virus Studies
- SARS-CoV-2 detection and testing
- Monoclonal and Polyclonal Antibodies Research
- Herpesvirus Infections and Treatments
- CRISPR and Genetic Engineering
- Cervical Cancer and HPV Research
- T-cell and Retrovirus Studies
- Hepatitis C virus research
- Animal Disease Management and Epidemiology
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Pluripotent Stem Cells Research
- CAR-T cell therapy research
- Virus-based gene therapy research
- Inflammation biomarkers and pathways
- interferon and immune responses
National Institute of Infectious Diseases
2015-2025
Kumamoto University
2019-2025
Tokyo University of Science
2002-2024
The University of Tokyo
2011-2021
Infectious Disease Research Institute
2012-2021
University of Tokyo Hospital
2018
Institute of Microbiology
2010-2017
Chinese Academy of Sciences
2010-2017
Tokyo Medical University
2016
Advanced Medical Research Institute
2004-2014
Antibody titers against SARS-CoV-2 slowly wane over time. Here, we examined how time affects antibody potency. To assess the impact of maturation on durable neutralizing activity original and emerging variants concern (VOCs), analyzed receptor binding domain (RBD)-specific IgG antibodies in convalescent plasma taken 1-10 months after infection. Longitudinal evaluation total RBD revealed declining but improved neutralization potency per to SARS-CoV-2, indicative response maturation....
Antigenic peptides recognized by virus-specific cytotoxic T lymphocytes (CTLs) are presented major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and the peptide selection presentation strategy of host has been studied to guide our understanding cellular immunity vaccine development. Here, a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N) protein-derived CTL epitope, N1 (QFKDNVILL), restricted HLA-A*2402 was identified series...
Effective vaccines are essential for the control of coronavirus disease 2019 (COVID-19) pandemic. Currently developed inducing severe acute respiratory syndrome 2 (SARS-CoV-2) spike (S)-antigen-specific neutralizing antibodies (NAbs) effective, but appearance NAb-resistant S variant viruses is great concern. A vaccine S-independent or NAb-independent SARS-CoV-2 may contribute to containment these variants. Here, we investigate efficacy an intranasal expressing viral non-S antigens against...
ABSTRACT Investigating escape mechanisms of human immunodeficiency virus type 1 (HIV-1) from cytotoxic T lymphocytes (CTLs) is essential for understanding the pathogenesis HIV-1 infection and developing effective vaccines. To study processing presentation known CTL epitopes, we prepared Epstein-Barr virus-transformed B cells that endogenously express gag gene six field isolates by adopting an env/nef -deletion vector pseudotyped with vesicular stomatitis G protein then tested them...
The discovery of induced pluripotent stem cells (iPSCs) has created promising new avenues for therapies in regenerative medicine. However, the tumorigenic potential undifferentiated iPSCs is a major safety concern clinical translation. To address this issue, we demonstrated efficacy suicide gene therapy by introducing inducible caspase-9 (iC9) into iPSCs. Activation iC9 with specific chemical inducer dimerization (CID) initiates caspase cascade that eliminates and tumors originated from We...
HLA‐A, ‐C, ‐B, and ‐DRB1 genotypes were analyzed in 178 Japanese COVID‐19 patients to investigate the association of HLA with severe COVID‐19. Analysis 32 common alleles at four loci revealed a significant between HLA‐DRB1*09:01 (odds ratio [OR], 3.62; 95% CI, 1.57–8.35; p = 0.00251 [permutation value 0.0418]) when age, sex, other DRB1 locus adjusted. The DRB1*09:01 allele was more significantly associated risk for compared preexisting medical conditions such as hypertension, diabetes,...
ABSTRACT The emergence of syncytium-inducing (SI) variants human immunodeficiency virus type 1 (HIV-1) in infected individuals is an indicator poor prognosis and often correlated with faster CD4 + cell depletion rapid disease progression. Interleukin-4 (IL-4) a pleiotropic cytokine various immune-modulating functions including induction immunoglobulin E (IgE) production B cells, down-regulation CCR5 (a coreceptor for HIV-1 non-SI [NSI] strains), up-regulation CXCR4 SI variants). Here we show...
ABSTRACT To evaluate the immunogenicity of human immunodeficiency virus (HIV) type 1 p55 gag virus-like particles (VLPs) released by budding from yeast spheroplasts, we have analyzed effects VLPs on monocyte-derived dendritic cells (DCs). Yeast were efficiently incorporated into DCs via both macropinocytosis and endocytosis mediated mannose-recognizing receptors, but not mannose receptor. The uptake induced DC maturation enhanced cytokine production, notably, interleukin-12 p70. We showed...
Abstract Immune response enhanced by therapeutic HIV‐1 vaccine may control viral proliferation after discontinuation of highly active antiretroviral therapy (HAART). Although which strategies for vaccination are feasible remains controversial, application dendritic cells (DCs) as a adjuvant represents promising approach to improving deteriorated immune function in HIV‐1‐infected individuals. The safety and efficacy DC‐based loaded with HIV‐1‐derived cytotoxic T lymphocytes (CTL) peptides...
The molecular mechanisms for IL2 gene–specific dysregulation during chronic human immunodeficiency virus type 1 (HIV-1) infection are unknown. Here, we investigated the role of DNA methylation in suppressing interleukin 2 (IL-2) expression memory CD4+ T cells HIV-1 infection. We observed that CpG sites promoter were fully methylated naive and significantly demethylated populations. Interestingly, found had a terminally differentiated phenotype expressed CD57 increased relative to less...
HIV-1 infected individuals under antiretroviral therapy can control viremia but often develop non-AIDS diseases such as cardiovascular and metabolic disorders. Gut microbiome dysbiosis has been indicated to be associated with progression of these diseases. Analyses gut/fecal in individual regions are important for our understanding pathogenesis infections. However, data on not yet accumulated West Africa. In the present study, we examined fecal compositions adults Ghana, where approximately...
ABSTRACT CCR5 is an essential coreceptor for the cellular entry of R5 strains human immunodeficiency virus type 1 (HIV-1). CCR5-893(−) a single-nucleotide deletion mutation which observed exclusively in Asians (M. A. Ansari-Lari, et al., Nat. Genet. 16:221–222, 1997). This mutant gene produces lacks entire C-terminal cytoplasmic tail. To assess effect on HIV-1 infection, we generated recombinant Sendai expressing and compared its activity with that wild-type CCR5. Although has intact...
We investigated the crystal structure of an HLA-A*2402-restricted CTL epitope in HIV-1 nef gene (Nef134-10) before (pHLA) or after TCR docking. The wild type and two escape mutants were included study. Y135F was early-appearing major mutation, while F139L a late-appearing mutation which selected patients without Y135F. F139 eminent feature Nef134-10 epitope. Wild type-specific less fit to mutant suggesting that is from against Although disrupted hydrogen bond HLA-A*2402 His70, newly formed...
ABSTRACT HIV-1 patients continue to remain at an abnormal immune status despite prolonged combination antiretroviral therapy (cART), which results in increased risk of non-AIDS-related diseases. Given the growing recognition importance understanding and controlling residual virus patients, additional virological markers monitor infected cells are required. However, viral replication circulating is much poorer than that lymph nodes, absence distinguish these from uninfected blood. In this...
Abstract An expanded myeloid cell compartment is a hallmark of severe coronavirus disease 2019 (COVID-19). However, data regarding expansion have been collected in Europe, where the mortality rate by COVID-19 greater than those other regions including Japan. Thus, characteristics COVID-19-induced subsets remain largely unknown with low rates. Here, we analyzed cellular dynamics myeloid-derived suppressor (MDSC) and examined whether any them correlate severity prognosis, using blood samples...
Adoptive immunotherapy has emerged as a powerful approach to cure cancer and chronic infections. Currently, the generation of massive number T cells that provide long-lasting immunity is challenged by exhaustion differentiation-associated senescence, which inevitably arise during in vitro cloning expansion. To circumvent these problems, several studies have proposed an induced pluripotent stem cell (iPSC)-mediated rejuvenation strategy revitalize exhausted/senescent clones. Because...
Human T-cell leukemia virus type 1 (HTLV-1) induces chronic long-term latent infection that can cause fatal diseases, including adult leukemia. HTLV-1 production is poor and undetectable during the asymptomatic phase of infection. Virus-host immune interaction in has not been fully determined. In present study, virus-specific antibody responses carriers (n = 77) were investigated. Neutralizing significantly higher individuals with anti-Env SU (gp46) levels positively correlated proviral...
Cervical intraepithelial neoplasia (CIN), a precursor lesion to cervical cancer, is caused by high-risk human papillomavirus (HPV); high-grade CIN lesions (CIN2-3) are precancerous and require treatment. No globally approved therapy available for CIN2-3 This study placebo-controlled randomized clinical trial of GLBL101c treatment CIN2 in 40 patients with HPV16-positive who were 1:1 receive (1 g/daily) or placebo 5 days at 1, 2, 4, 8 weeks. differences noted between the groups patient...
Abstract Background Although many human papillomavirus (HPV)–targeted therapeutic vaccines have been examined for efficacy in clinical trials, none translated into use. These previous agents were mostly administered by intramuscular or subcutaneous injection to induce systemic immunity. We investigated the safety and of an HPV-16 E7-expressing lacticaseibacillus-based oral vaccine. Methods In a double-blind, placebo-controlled, randomized trial, total 165 patients with HPV-16–positive...
Although Japan is classified as a country with low prevalence of human immunodeficiency virus type 1 (HIV-1), domestic sexual transmission has been increasing steadily. Because 70% the Japanese population expresses HLA-A24 (genotype HLA-A*2402), we wished to assess effect dominant HLA on evolution and HIV-1 among population. Twenty-three out 25 A24-positive patients had Y-to-F substitution at second position [Nef138-10(2F)] in an immunodominant A24-restricted CTL epitope their nef gene...
Background This study aimed to clarify how SARS-CoV-2 RNAemia is related COVID-19 critical condition development and mortality in comparison with other predictive markers scoring systems. Methods a retrospective cohort conducted at Yokohama Municipal Citizen’s Hospital National Institute of Infectious Diseases. We recruited adult patients admitted between March 2020 January 2021. compared clinical status on admission including systems such as the 4C Mortality, CURB-65, A-DROP, well C t value...
Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target infection peripheral blood central nervous system (CNS), plasma proteomics were applied untreated chronic HIV-infected individuals different levels virus control.
Chronic HIV-1 infection is characterized by immune cell dysfunctions driven chronic activation. Plasma viral load (VL) closely correlated with disease progression and the level of However, mechanism which persistent presence damages cells still not fully understood. To evaluate how affects disruption T cell-mediated responses during we determined functional profiles from subjects infection. We measured capacity peripheral blood mononuclear (PBMCs) to produce 25 specific cytokines in response...