Development of a Monoclonal Antibody Targeting HTLV-1 Envelope gp46 Glycoprotein and Its Application to Near-Infrared Photoimmuno-Antimicrobial Strategy

Viruses. 2022 Sep 29;14(10):2153. doi: 10.3390/v14102153.

Abstract

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.

Keywords: HTLV-1; IR700; monoclonal antibody; near infrared photoimmuno-antimicrobial strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Gene Products, env
  • Glycoproteins
  • Human T-lymphotropic virus 1*
  • Humans
  • Liposomes
  • Mice
  • Proline
  • Recombinant Proteins
  • Retroviridae Proteins, Oncogenic

Substances

  • Retroviridae Proteins, Oncogenic
  • Antibodies, Monoclonal
  • Liposomes
  • Gene Products, env
  • Recombinant Proteins
  • Glycoproteins
  • Proline

Grants and funding

This work was supported in part by grants from the Japan Agency for Medical Research and Development (AMED) (grant number JP22fk0108125 to A.R.).