Abstract 933: Effect of mRNA vaccine-induced neutralizing antibodies on human T-cell leukemia virus type-1

Abstract Introduction/Background: Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus linked to severe conditions such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The absence of a preventative therapy for HTLV-1 represents a significant gap in public health. Our lab has developed a codon-optimized HTLV-1 envelope (Env) mRNA vaccine encapsulated in lipid nanoparticles (LNP), which demonstrated partial protection in a rabbit model. However, further research is required to optimize its efficacy. Methods: The study involved evaluating the neutralizing antibody response induced by the HTLV-1 mRNA vaccine against HTLV-1a and HTLV-1c in various assays. Western blot analysis assessed the expression of the gp46 envelope glycoprotein and HIV capsid protein p24 in HEK 293T cells transfected with HTLV-1a or HTLV-1c Env plasmids. Fusion assays measured cell-cell fusion using mCherry fluorescent protein in 293T cells, with the effects of IgG serum from infected rabbits assessed. Virus titration involved VSV-HTLV Env and VSV-eGFP to evaluate viral infection inhibition. Neutralizing antibody assays tested IgG from HTLV-infected and non-infected rabbits to determine the extent of viral inhibition. Results: Expression of gp46 and HIV-1 p24 was confirmed in 293T cells co-transfected with HTLV-1a or HTLV-1c Env plasmids. Fusion assays indicated that IgG from infected rabbits effectively inhibited fusion in HTLV-1a and HTLV-1c Env-expressing cells. Virus titration presented significant inhibition of viral infection by IgG from HTLV-infected rabbits, with an IC50 of 0.05 µg. Conclusion: The study demonstrates that the HTLV-1 envelope mRNA vaccine induces neutralizing antibodies that can inhibit HTLV-1 infection and fusion processes. These findings support the potential of the mRNA vaccine as a preventive measure against HTLV-1-associated diseases and provide a basis for further research to optimize vaccine efficacy. Citation Format: Diandra Frias, Nehla Banu, Xiaogang Cheng, Ancy Joseph, Zhuoming Liu, Sean Whelan, Lee Ratner, Lee Ratner. Effect of mRNA vaccine-induced neutralizing antibodies on human T-cell leukemia virus type-1. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 933.