Mizuguchi Mariko, Takahashi Yoshiaki, Tanaka Reiko, Fukushima Takuya, Tanaka Yuetsu
Department of Immunology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa 903-0215, Japan.
Laboratory of Hematoimmunology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa 903-0215, Japan.
Pathogens. 2020 Jan 27;9(2):82. doi: 10.3390/pathogens9020082.
Approximately one-tenth of the 10 million individuals living with human T-cell leukemia virus type-1 (HTLV-1) worldwide live in Japan. Most of these infected individuals live in the southwest region of Japan, including Okinawa prefecture; however, currently no prophylactic vaccine against HTLV-1 infection is available. For preventing the HTLV-1 spread, we previously generated a humanized monoclonal antibody (hu-LAT-27) that mediates both neutralization and antibody-dependent cellular cytotoxicity (ADCC). The neutralization epitope of LAT-27 is a linear amino acid sequence from residue 191 to 196 (Leu-Pro-His-Ser-Asn-Leu) of the HTLV-1 envelope gp46 protein. Here, we found that the LAT-27 epitope is well conserved among HTLV-1 clinical isolates prevalent in Okinawa. The hu-LAT-27 treatment inhibited syncytium formation by these clinical HTLV-1 isolates. Although an amino acid substitution at residue 192 in the LAT-27 epitope from proline to serine was found in a few HTLV-1 isolates, hu-LAT-27 could still react with a synthetic peptide carrying this amino acid substitution. These findings demonstrate the wide spectrum of hu-LAT-27 reactivity, suggesting that hu-LAT-27 may be a candidate drug for prophylactic passive immunization against HTLV-1 infection.
全球约1000万感染人类T细胞白血病病毒1型(HTLV-1)的人中,约十分之一生活在日本。这些受感染个体大多生活在日本西南部地区,包括冲绳县;然而,目前尚无针对HTLV-1感染的预防性疫苗。为防止HTLV-1传播,我们之前制备了一种人源化单克隆抗体(hu-LAT-27),它能介导中和作用和抗体依赖性细胞毒性(ADCC)。LAT-27的中和表位是HTLV-1包膜糖蛋白gp46第191至196位残基(亮氨酸-脯氨酸-组氨酸-丝氨酸-天冬酰胺-亮氨酸)的线性氨基酸序列。在此,我们发现LAT-27表位在冲绳流行的HTLV-1临床分离株中高度保守。hu-LAT-27处理可抑制这些临床HTLV-1分离株诱导的合胞体形成。虽然在少数HTLV-1分离株中发现LAT-27表位第192位残基的脯氨酸被丝氨酸取代,但hu-LAT-27仍能与携带此氨基酸取代的合成肽发生反应。这些发现证明了hu-LAT-27反应性的广谱性,提示hu-LAT-27可能是预防HTLV-1感染的被动免疫候选药物。