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

被引：14

作者：

Kashiwakura, Yuji ^{[1
]}

Baatartsogt, Nemekhbayar ^{[1
]}

Yamazaki, Shoji ^{[2
]}

Nagao, Azusa ^{[3
]}

Amano, Kagehiro ^{[4
]}

Suzuki, Nobuaki ^{[5
]}

Matsushita, Tadashi ^{[5
]}

Sawada, Akihiro ^{[6
]}

Higasa, Satoshi ^{[6
]}

Yamasaki, Naoya ^{[7
]}

Fujii, Teruhisa ^{[7
]}

Ogura, Taemi ^{[8
]}

Takedani, Hideyuki ^{[9
]}

Taki, Masashi ^{[10
]}

Matsumoto, Takeshi ^{[11
]}

Yamanouchi, Jun ^{[12
]}

Sakai, Michio ^{[13
]}

Nishikawa, Masako ^{[14
]}

Yatomi, Yutaka ^{[14
]}

Yada, Koji ^{[15
]}

Nogami, Keiji ^{[15
]}

Watano, Ryota ^{[16
]}

Hiramoto, Takafumi ^{[1
]}

Hayakawa, Morisada ^{[1
,17
]}

Kamoshita, Nobuhiko ^{[1
,17
]}

Kume, Akihiro ^{[2
,17
]}

Mizukami, Hiroaki ^{[16
,17
]}

Ishikawa, Shizukiyo ^{[18
]}

Sakata, Yoichi ^{[1
]}

Ohmori, Tsukasa ^{[1
,17
]}

机构：

[1] Jichi Med Univ, Sch Med, Dept Biochem, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan

[2] Jichi Med Univ Hosp, Clin Res Ctr, 3311-1 Yakushiji, Shimotsuke, Tochigi, Japan

[3] Ogikubo Hosp, Dept Blood Coagulat, 3-1-24 Imagawa, Tokyo 1670035, Japan

[4] Tokyo Med Univ Hosp, Dept Lab Med, Shinjuku Ku, 6-7-1 Nishishinjuku, Tokyo 1600023, Japan

[5] Nagoya Univ Hosp, Dept Transfus Med, Showa Ku, 65 Tsurumai, Nagoya, Aichi 4668560, Japan

[6] Hyogo Med Univ, Dept Resp Med & Hematol, 1-1 Mukogawa, Nishinomiya, Hyogo 6338501, Japan

[7] Hiroshima Univ Hosp, Hemophilia Treatment Ctr, Minami Ku, 1-2-3 Kasumi, Hiroshima, Hiroshima 7348551, Japan

[8] Shizuoka Childrens Hosp, Hemophilia Treatment Ctr, 860 Urushiyama, Shizuoka, Shizuoka 4208660, Japan

[9] Univ Tokyo, IMSUT Hosp, Dept Joint Surg, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan

[10] St Marianna Univ, Dept Pediat, Sch Med Hosp, Miyamae Ku, 2-16-1 Sugao, Kawasaki, Kanagawa 2168511, Japan

[11] Mie Univ Hosp, Dept Transfus Med & Cell Therapy, 2-174 Edobashi, Tsu, Mie 5148507, Japan

[12] Ehime Univ Hosp, Div Blood Transfus & Cell Therapy, 454 Shitsukawa, Toon, Ehime 7910204, Japan

[13] Munakata Suikokai Gen Hosp, Dept Pediat, 5-7-1 Himakino, Fukuoka, Fukuoka 8113298, Japan

[14] Univ Tokyo Hosp, Dept Clin Lab, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan

[15] Nara Med Univ Hosp, Dept Pediat, 840 Shijo, Kashihara, Nara 6348522, Japan

[16] Jichi Med Univ, Ctr Mol Med, Div Genet Therapeut, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan

[17] Jichi Med Univ, Ctr Gene Therapy Res, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan

[18] Jichi Med Univ, Ctr Informat, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan

来源：

MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT | 2022年 / 27卷

关键词：

GENE-THERAPY; IMMUNE-RESPONSES; FACTOR-IX; PREVALENCE; SEROTYPES; HEALTHY; LIVER; AAV8;

D O I：

10.1016/j.omtm.2022.10.014

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Adeno-associated virus (AAV) vectors are promising modal-ities 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 clin-ical trials with AAV vectors. Hence, updating the seropreva-lence 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-pos-itive 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 in vitro, was mostly found in people in their 60s or of older age. The multivariate analysis suggested that "60s or older age" was the only independent factor related to the high titer of NAbs. Conversely, a large proportion of younger hemo-philiacs was seronegative, rendering them eligible for AAV-mediated gene therapy in Japan. Compared with our previous study, the peak of seroprevalences has shifted to older populations, indicating that natural AAV exposure in the elderly occurred in their youth but not during the last decade.

引用

页码：404 / 414

页数：11

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