A Potential of an Anti-HTLV-I gp46 Neutralizing Monoclonal Antibody (LAT-27) for Passive Immunization against Both Horizontal and Mother-to-Child Vertical Infection with Human T Cell Leukemia Virus Type-I

Hideki Fujii,Takuya Miyagi,Mamoru Shimizu,Yuetsu Tanaka,Reiko Tanaka,Yoshiaki Takahashi,Marie Kunihiro

doi:10.3390/v8020041

Abstract

Although the number of human T-cell leukemia virus type-I (HTLV-I)-infected individuals in the world has been estimated at over 10 million, no prophylaxis vaccines against HTLV-I infection are available. In this study, we took a new approach for establishing the basis of protective vaccines against HTLV-I. We show here the potential of a passively administered HTLV-I neutralizing monoclonal antibody of rat origin (LAT-27) that recognizes epitopes consisting of the HTLV-I gp46 amino acids 191–196. LAT-27 completely blocked HTLV-I infection in vitro at a minimum concentration of 5 μg/mL. Neonatal rats born to mother rats pre-infused with LAT-27 were shown to have acquired a large quantity of LAT-27, and these newborns showed complete resistance against intraperitoneal infection with HTLV-I. On the other hand, when humanized immunodeficient mice were pre-infused intravenously with humanized LAT-27 (hu-LAT-27), all the mice completely resisted HTLV-I infection. These results indicate that hu-LAT-27 may have a potential for passive immunization against both horizontal and mother-to-child vertical infection with HTLV-I.

Highlights

Human T-cell leukemia virus type I (HTLV-I) [1,2] causes both neoplastic and inflammatory diseases, including adult T-cell leukemia (ATL) [3,4] and human T-cell leukemia virus type-I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) [5,6]
On the way to establishing a basis for vaccine development against HTLV-I, we previously reported that our anti-gp46 neutralizing monoclonal antibodies (mAbs) (LAT-27)
It has been demonstrated that rats are relatively permissive for in vivo infection with HTLV-I

Summary

Introduction

Human T-cell leukemia virus type I (HTLV-I) [1,2] causes both neoplastic and inflammatory diseases, including adult T-cell leukemia (ATL) [3,4] and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) [5,6]. The number of HTLV-I-infected individuals in the world has been estimated at over 10 million [7]. No prophylaxis vaccines or drugs against HTLV-I infection are available. HTLV-I is transmitted through contact with bodily fluids containing infected cells, most often from mother to child through breast milk or via blood transfusion. The HTLV-I envelope spike consists of two glycoproteins, cell surface gp and trans-membrane gp21 [9], both of which are essential for HTLV-I entry into cells [10]

Methods

Results

Conclusion