TY - JOUR
T1 - Nasal vaccine delivery attenuates brain pathology and cognitive impairment in tauopathy model mice
AU - Takeuchi, Hiroki
AU - Imamura, Keiko
AU - Ji, Bin
AU - Tsukita, Kayoko
AU - Enami, Takako
AU - Takao, Keizo
AU - Miyakawa, Tsuyoshi
AU - Hasegawa, Masato
AU - Sahara, Naruhiko
AU - Iwata, Nobuhisa
AU - Inoue, Makoto
AU - Hara, Hideo
AU - Tabira, Takeshi
AU - Ono, Maiko
AU - Trojanowski, John Q.
AU - Lee, Virginia M.Y.
AU - Takahashi, Ryosuke
AU - Suhara, Tetsuya
AU - Higuchi, Makoto
AU - Inoue, Haruhisa
N1 - Funding Information:
We thank Takashi Usui, Shio Kobayashi, Kazuo Nakanishi, Takashi Sakurai for their scientific discussions, and Kumiko Imai for administrative support. This work was supported in part by grants from Grants-in-Aid for Molecular Imaging Program and Japan Advanced Molecular Imaging Program to H.I., T.S., and M.H., from CREST to H.I. and T.S., from a Grant-in-Aid for Scientific Research on Innovative Area “Foundation of Synapse and Neurocircuit Pathology” (22110007) to H.I. from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and Scientific Research on Innovative Areas “Brain Environment” (23111009) to M.H. from MEXT, Japan, and Grant-in-Aid for Scientific Research (18H02717, 18K18452) to H.I. from MEXT, Japan, and Grant-in-Aid for Scientific Research (17K10297) to K.I. V.M.-Y.L. and J.Q.T. are supported by AG-17586.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85082430954&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082430954&partnerID=8YFLogxK
U2 - 10.1038/s41541-020-0172-y
DO - 10.1038/s41541-020-0172-y
M3 - Article
AN - SCOPUS:85082430954
VL - 5
JO - npj Vaccines
JF - npj Vaccines
SN - 2059-0105
IS - 1
M1 - 28
ER -