Development of A HTLV-1 Vaccine

PROJECT SUMMARY
For this proposal we intend to develop a novel vaccine to prevent and possibly treat Human T cell leukemia
virus type-1 (HTLV-1) associated diseases. HTLV-1 is a human retrovirus that is the causative agent of a
malignant T CD4+ cell lymphoproliferation referred to as Adult T cell leukemia/lymphoma (ATLL), as well as
several inflammatory disorders with the most problematic being human myelopathy/tropical spastic paraparesis
(HAM/TSP). HTLV-1 infection is endemic in many areas around the world including southern Japan, the southern
United States, central Australia, the Caribbean, South America, equatorial Africa, and the middle East. Over 10
million people may be infected worldwide. It is estimated that approximately 5% of HTLV-1 positive individuals
will develop ATL, and 2% HAM/TSP. Seropositive rates in certain areas reach 20–40% among people aged over
50 years. With millions affected worldwide, HTLV-1 is a major problem in endemic communities and remarkably,
there are no effective vaccine or treatment options to prevent ATL or HAM/TSP afflicted individuals. Given
this, aim to develop and test the efficacy of a novel vaccine to prevent HTLV1-mediated disease.
Aim 1: To evaluate the immunogenicity, in immunocompetent murine models, including mice with a humanized
immune system (NSG™-SGM3) VSV-based vaccine vectors that express the HTLV-1 glycoprotein and
regulatory proteins TAX and HBZ (VSV-gp62-∆HT). The ability of our candidate vaccine to generate neutralizing
antibodies to the glycoprotein will be analyzed, as well as the production of cytotoxic T cells (CTLs) to gp62, TAX
and HBZ.
Aim 2: We aim to compare whether our vaccine can be used to prevent HTLV-1 transformation associated
disease. This approach will include establishing whether VSV-gp62-∆HT can prevent the establishment of HTLV-
1-assocated leukemia/lymphoma in NSG™-SGM3 mice. Our objectives are to collate sufficient information to
warrant the consideration of a variety of Phase I trials to prevent HTLV-1 -associated disease.

Grant Number: 7R01CA252049-05
NIH Institute/Center: NIH
Principal Investigator: Glen Barber