Abstract
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.
Highlights
The number of human T-cell leukemia virus type 1 (HTLV-1)-infected individuals worldwide is estimated to be around 10 million [1]
To determine whether the neutralization domain is conserved among various clinical isolates, HTLV-1 genomic sequences were analyzed using 16 newly established HTLV-1-infected cell lines originating from various subtypes of patients with adult T-cell leukemia/lymphoma (ATL) living in Okinawa (Table 1)
We further investigated the conservation of the LAT-27 epitope among HTLV-1 produced by primary peripheral blood mononuclear cells (PBMCs) and lymph node (LN) cells from patients with various subtypes of ATL or from asymptomatic carriers (Table 2) using flow cytometry (FCM)
Summary
The number of human T-cell leukemia virus type 1 (HTLV-1)-infected individuals worldwide is estimated to be around 10 million [1]. HTLV-1 causes neoplastic and inflammatory diseases, such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), respectively [2,3,4,5]. HTLV-1 is transmitted through breastfeeding and sexual contact via the influx of bodily fluids containing infected cells. HTLV-1 infection has been developed to date. As humanized or human monoclonal antibodies (mAb) have been demonstrated to be safe and effective in various areas of medicine, passive immunization with an HTLV-1 neutralizing mAb has been suggested as a potentially effective strategy for preventing the spread of HTLV-1 [6,7,8,9,10].
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