Nasal vaccine delivery attenuates brain pathology and cognitive impairment in tauopathy model mice

Hiroki Takeuchi, Keiko Imamura, Bin Ji, Kayoko Tsukita, Takako Enami, Keizo Takao, Tsuyoshi Miyakawa, Masato Hasegawa, Naruhiko Sahara, Nobuhisa Iwata, Makoto Inoue, Hideo Hara, Takeshi Tabira, Maiko Ono, John Q. Trojanowski, Virginia M.Y. Lee, Ryosuke Takahashi, Tetsuya Suhara, Makoto Higuchi, Haruhisa Inoue

Research output: Contribution to journalArticle

Abstract

Pathological aggregates of tau proteins accumulate in the brains of neurodegenerative tauopathies including Alzheimer’s disease and frontotemporal lobar degeneration (FTLD-tau). Although immunotherapies of these disorders against tau are emerging, it is unknown whether nasal delivery, which offers many benefits over traditional approaches to vaccine administration, is effective or not for tauopathy. Here, we developed vaccination against a secreted form of pathological tau linked to FTLD-tau using a Sendai virus (SeV) vector infectious to host nasal mucosa, a key part of the immune system. Tau vaccines given as nasal drops induced tissue tau-immunoreactive antibody production and ameliorated cognitive impairment in FTLD-tau model mice. In vivo imaging and postmortem neuropathological assays demonstrated the suppression of phosphorylated tau accumulation, neurotoxic gliosis, and neuronal loss in the hippocampus of immunized mice. These findings suggest that nasal vaccine delivery may provide a therapeutic opportunity for a broad range of populations with human tauopathy.

Original languageEnglish
Article number28
Journalnpj Vaccines
Volume5
Issue number1
DOIs
Publication statusPublished - 01-12-2020

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology
  • Infectious Diseases
  • Pharmacology (medical)

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    Takeuchi, H., Imamura, K., Ji, B., Tsukita, K., Enami, T., Takao, K., Miyakawa, T., Hasegawa, M., Sahara, N., Iwata, N., Inoue, M., Hara, H., Tabira, T., Ono, M., Trojanowski, J. Q., Lee, V. M. Y., Takahashi, R., Suhara, T., Higuchi, M., & Inoue, H. (2020). Nasal vaccine delivery attenuates brain pathology and cognitive impairment in tauopathy model mice. npj Vaccines, 5(1), [28]. https://doi.org/10.1038/s41541-020-0172-y