The seroprevalence of neutralizing antibodies against the adeno-associated virus capsids in Japanese hemophiliacs.

antibodies dependovirus genetic therapy neutralizing treatment outcome virus vector

Journal

Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857

Informations de publication

Date de publication:
08 Dec 2022
Historique:
received: 21 06 2022
accepted: 24 10 2022
entrez: 16 11 2022
pubmed: 17 11 2022
medline: 17 11 2022
Statut: epublish

Résumé

Adeno-associated virus (AAV) vectors are promising modalities of gene therapy to address unmet medical needs. However, anti-AAV neutralizing antibodies (NAbs) hamper the vector-mediated therapeutic effect. Therefore, NAb prevalence in the target population is vital in designing clinical trials with AAV vectors. Hence, updating the seroprevalence of anti-AAV NAbs, herein we analyzed sera from 100 healthy individuals and 216 hemophiliacs in Japan. In both groups, the overall seroprevalence against various AAV serotypes was 20%-30%, and the ratio of the NAb-positive population increased with age. The seroprevalence did not differ between healthy participants and hemophiliacs and was not biased by the concomitant blood-borne viral infections. The high neutralizing activity, which strongly inhibits the transduction with all serotypes

Identifiants

pubmed: 36381300
doi: 10.1016/j.omtm.2022.10.014
pii: S2329-0501(22)00156-5
pmc: PMC9661668
doi:

Types de publication

Journal Article

Langues

eng

Pagination

404-414

Informations de copyright

© 2022 The Author(s).

Déclaration de conflit d'intérêts

All authors have no competing financial interests to declare.

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Auteurs

Yuji Kashiwakura (Y)

Department of Biochemistry, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, Japan.

Nemekhbayar Baatartsogt (N)

Department of Biochemistry, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, Japan.

Shoji Yamazaki (S)

Clinical Research Center, Jichi Medical University Hospital, 3311-1 Yakushiji, Shimotsuke, Tochigi, Japan.

Azusa Nagao (A)

Department of Blood Coagulation, Ogikubo Hospital, 3-1-24 Imagawa, Suginami, Tokyo 167-0035, Japan.

Kagehiro Amano (K)

Department of Laboratory Medicine, Tokyo Medical University Hospital, 6-7-1, Nishishinjuku, Shinjuku, Tokyo 160-0023, Japan.

Nobuaki Suzuki (N)

Department of Transfusion Medicine, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, Aichi 466-8560, Japan.

Tadashi Matsushita (T)

Department of Transfusion Medicine, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, Aichi 466-8560, Japan.

Akihiro Sawada (A)

Department of Respiratory Medicine and Hematology, Hyogo Medical University, 1-1 Mukogawa, Nishinomiya, Hyogo 633-8501, Japan.

Satoshi Higasa (S)

Department of Respiratory Medicine and Hematology, Hyogo Medical University, 1-1 Mukogawa, Nishinomiya, Hyogo 633-8501, Japan.

Naoya Yamasaki (N)

Hemophilia Treatment Center, Hiroshima University Hospital, 1-2-3 Kasumi, Minami, Hiroshima, Hiroshima 734-8551, Japan.

Teruhisa Fujii (T)

Hemophilia Treatment Center, Hiroshima University Hospital, 1-2-3 Kasumi, Minami, Hiroshima, Hiroshima 734-8551, Japan.

Taemi Ogura (T)

Hemophilia Treatment Center, Shizuoka Children's Hospital, 860 Urushiyama, Aoi, Shizuoka, Shizuoka 420-8660, Japan.

Hideyuki Takedani (H)

Department of Joint Surgery, IMSUT Hospital, The University of Tokyo, 4-6-1 Shirokanedai, Minato, Tokyo 108-8639, Japan.

Masashi Taki (M)

Department of Pediatrics, St. Marianna University School of Medicine Hospital, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8511, Japan.

Takeshi Matsumoto (T)

Department of Transfusion Medicine and Cell Therapy, Mie University Hospital, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.

Jun Yamanouchi (J)

Division of Blood Transfusion and Cell Therapy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime 791-0204, Japan.

Michio Sakai (M)

Department of Pediatrics, Munakata Suikokai General Hospital, 5-7-1 Himakino, Fukutsu, Fukuoka 811-3298, Japan.

Masako Nishikawa (M)

Department of Clinical Laboratory, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.

Yutaka Yatomi (Y)

Department of Clinical Laboratory, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.

Koji Yada (K)

Department of Pediatrics, Nara Medical University Hospital, 840 Shijo, Kashihara, Nara 634-8522, Japan.

Keiji Nogami (K)

Department of Pediatrics, Nara Medical University Hospital, 840 Shijo, Kashihara, Nara 634-8522, Japan.

Ryota Watano (R)

Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.

Takafumi Hiramoto (T)

Department of Biochemistry, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, Japan.

Morisada Hayakawa (M)

Department of Biochemistry, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, Japan.
Center for Gene Therapy Research, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.

Nobuhiko Kamoshita (N)

Department of Biochemistry, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, Japan.
Center for Gene Therapy Research, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.

Akihiro Kume (A)

Clinical Research Center, Jichi Medical University Hospital, 3311-1 Yakushiji, Shimotsuke, Tochigi, Japan.
Center for Gene Therapy Research, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.

Hiroaki Mizukami (H)

Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Center for Gene Therapy Research, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.

Shizukiyo Ishikawa (S)

Center for Information, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.

Yoichi Sakata (Y)

Department of Biochemistry, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, Japan.

Tsukasa Ohmori (T)

Department of Biochemistry, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, Japan.
Center for Gene Therapy Research, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.

Classifications MeSH