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Otorhinolaryngologic Diseases

Immune System Diseases

Digestive System Disorders

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Disease Domain	Count

Hemic and Lymphatic Diseases	1
Infectious Diseases	1
Immune System Diseases	1

Top 5 Drug Type	Count

Small molecule drug	1

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GR(Glucocorticoid receptor)	1

Cationic cholesteryl-group-bearing pullulan nanogel (cCHP-nanogel) is an effective drug-delivery system for nasal vaccines. However, cCHP-nanogel-based nasal vaccines might access the central nervous system due to its close proximity via the olfactory bulb in the nasal cavity. Using real-time quantitative tracking of the nanogel-based nasal botulinum neurotoxin and pneumococcal vaccines, we previously confirmed the lack of deposition of vaccine antigen in the cerebrum or olfactory bulbs of mice and non-human primates (NHPs), rhesus macaques. Here, we used positron emission tomography to investigate the biodistribution of the drug-delivery system itself, cCHP-nanogel after mice and NHPs were nasally administered with ¹⁸F-labeled cCHP nanogel. The results generated by the PET analysis of rhesus macaques were consistent with the direct counting of radioactivity due to ¹⁸F or ¹¹¹In in dissected mouse tissues. Thus, no depositions of cCHP-nanogel were noted in the cerebrum, olfactory bulbs, or eyes of both species after nasal administration of the radiolabeled cCHP-nanogel compound. Our findings confirm the safe biodistribution of the cCHP-nanogel-based nasal vaccine delivery system in mice and NHPs.

01 Jan 2023·Frontiers in immunology

Application of spatial transcriptomics analysis using the Visium system for the mouse nasal cavity after intranasal vaccination.

Article

Author: Toyama, Sakiko ; Hashimoto, Shinichi ; Matsumoto, Yusuke ; Honda, Tomoko ; Yamaji, Kenzaburo ; Kikkawa, Yoshiaki ; Kawaji, Hideya ; Kohara, Michinori ; Iwabuchi, Sadahiro ; Tokunaga, Yuko ; Miyazaki, Takashi

Intranasal vaccines that elicit mucosal immunity are deemed effective against respiratory tract infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their ability to induce humoral immunity characterized by immunoglobulin A (IgA) and IgG production is low. It has been reported that vaccination with a mixture of a viscous base carboxyvinyl polymer (CVP) and viral antigens induced robust systemic and mucosal immune responses. In this study, we analyzed the behavior of immunocompetent cells in the nasal cavity over time by spatial transcriptome profiling induced immediately after antigen vaccination using CVP. We established a method for performing spatial transcriptomics using the Visium system in the mouse nasal cavity and analyzed gene expression profiles within the nasal cavity after intranasal vaccination. Glycoprotein 2 (Gp2)-, SRY-box transcription factor 8 (Sox8)-, or Spi-B transcription factor (Spib)-expressing cells were increased in the nasal passage (NP) region at 3-6 hr after SARS-CoV-2 spike protein and CVP (S-CVP) vaccination. The results suggested that microfold (M) cells are activated within a short period of time (3-6 hr). Subsequent cluster analysis of cells in the nasal cavity showed an increase in Cluster 9 at 3-6 hr after intranasal vaccination with the S-CVP. We found that Il6 in Cluster 9 had the highest log2 fold values within the NP at 3-6 hr. A search for gene expression patterns similar to that of Il6 revealed that the log2 fold values of Edn2, Ccl20, and Hk2 also increased in the nasal cavity after 3-6 hr. The results showed that the early response of immune cells occurred immediately after intranasal vaccination. In this study, we identified changes in gene expression that contribute to the activation of M cells and immunocompetent cells after intranasal vaccination of mice with antigen-CVP using a time-series analysis of spatial transcriptomics data. The results facilitated the identification of the cell types that are activated during the initial induction of nasal mucosal immunity.

01 Jun 2021·VaccineQ3 · MEDICINE

A nanogel-based trivalent PspA nasal vaccine protects macaques from intratracheal challenge with pneumococci

Q3 · MEDICINE

Article

Author: Munesue, Yoshiko ; Hanari, Kouji ; Katakai, Yuko ; Nakano, Nozomi ; Mukerji, Reshmi ; Briles, David E ; Kiyono, Hiroshi ; Yamanoue, Tomoyuki ; Uchida, Yohei ; Akiyoshi, Kazunari ; Nakahashi-Ouchida, Rika ; Miyazaki, Takashi ; Yasutomi, Yasuhiro ; Sawada, Shin-Ichi ; Saito, Yuki ; Yuki, Yoshikazu ; Ogawa, Hiromi ; Umemoto, Shingo

Current polysaccharide-based pneumococcal vaccines are effective but not compatible with all serotypes of Streptococcus pneumoniae. We previously developed an adjuvant-free cationic nanogel nasal vaccine containing pneumococcal surface protein A (PspA), which is expressed on the surfaces of all pneumococcal serotypes. Here, to address the sequence diversity of PspA proteins, we formulated a cationic nanogel-based trivalent pneumococcal nasal vaccine and demonstrated the vaccine's immunogenicity and protective efficacy in macaques by using a newly developed nasal spray device applicable to humans. Nasal vaccination of macaques with cationic cholesteryl pullulan nanogel (cCHP)-trivalent PspA vaccine effectively induced PspA-specific IgGs that bound to pneumococcal surfaces and triggered complement C3 deposition. The immunized macaques were protected from pneumococcal intratracheal challenge through both inhibition of lung inflammation and a dramatic reduction in the numbers of bacteria in the lungs. These results demonstrated that the cCHP-trivalent PspA vaccine is an effective candidate vaccine against pneumococcal infections.

100 Deals associated with Toko Yakuhin Kogyo Co. Ltd.

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100 Translational Medicine associated with Toko Yakuhin Kogyo Co. Ltd.

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Pipeline

Pipeline Snapshot as of 22 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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