Development of a Monoclonal Antibody Targeting HTLV-1 Envelope gp46 Glycoprotein and Its Application to Near-Infrared Photoimmuno-Antimicrobial Strategy
Yasuyoshi Hatayama,
Yutaro Yamaoka,
Takeshi Morita,
Sundararaj Stanleyraj Jeremiah,
Kei Miyakawa,
Mayuko Nishi,
Yayoi Kimura,
Makoto Mitsunaga,
Tadayuki Iwase,
Hirokazu Kimura,
Naoki Yamamoto,
Akifumi Takaori-Kondo,
Hideki Hasegawa,
Akihide Ryo
Affiliations
Yasuyoshi Hatayama
Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
Yutaro Yamaoka
Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
Takeshi Morita
Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
Sundararaj Stanleyraj Jeremiah
Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
Kei Miyakawa
Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
Mayuko Nishi
Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
Yayoi Kimura
Advanced Medical Research Center, Yokohama City University, Yokohama 236-0004, Japan
Makoto Mitsunaga
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Minato 105-8461, Japan
Tadayuki Iwase
Research Center for Medical Sciences, The Jikei University School of Medicine, 3-25-8, Minato 105-8461, Japan
Hirokazu Kimura
Department of Health Science, Gunma Paz University Graduate School, Takasaki 370-0006, Japan
Naoki Yamamoto
Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa 272-8516, Japan
Akifumi Takaori-Kondo
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
Hideki Hasegawa
Center for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases, Musashimurayama 208-0011, Japan
Akihide Ryo
Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
Human T-cell leukemia virus type 1 (HTLV-1), a retrovirus, causes adult T-cell leukemia-lymphoma, HTLV-1 associated myelopathy/tropical spastic paraparesis, and HTLV-1 uveitis. Currently, no antiretroviral therapies or vaccines are available for HTLV-1 infection. This study aimed to develop an antibody against the HTLV-1 envelope protein (Env) and apply it to a near-infrared photoimmuno-antimicrobial strategy (NIR-PIAS) to eliminate HTLV-1 infected cells. We established mouse monoclonal antibodies (mAbs) against HTLV-1 Env by immunization with a complex of liposome and the recombinant protein. Detailed epitope mapping revealed that one of the mAbs bound to the proline-rich region of gp46 and exhibited no obvious neutralizing activity to inhibit viral infection. Instead, the mAb was rarely internalized intracellularly and remained on the cell surface of HTLV-1-infected cells. The antibody conjugated to the photosensitive dye IRDye700Dx recognized HTLV-1 infected cells and killed them following NIR irradiation. These results suggest that the novel mAb and NIR-PIAS could be developed as a new targeted therapeutic tool against HTLV-1 infected cells.
