Neutralizing antibodies and the pathogenesis of HTLV-1: Insights from clinical cohorts

Recent advances in mRNA-based vaccines have generated renewed interest in strategies to prevent Human T-Lymphotropic Virus type 1 (HTLV-1) infection. To explore this, we evaluated neutralizing antibody (NtAb) responses in 47 HTLV-1-infected individuals from Northwestern Argentina, an endemic region with high intrafamilial transmission and frequent cases of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Using a syncytium-inhibition assay, we quantified NtAb titers across three groups: asymptomatic carriers (n = 17), oligosymptomatic individuals (n = 20), and HAM/TSP patients (n = 10). NtAb titers ranged from 1/50 to 1/4000, with more than half of the samples showing titers between 1/500 and 1/1000. No significant differences were observed between groups, nor correlations with neurological signs, suggesting that NtAb responses are not predictive biomarkers for HTLV-1 disease progression. Also, our results demonstrated that NtAb generated in vivo would not be protective for the development of TSP/HAM. These findings indicate that while neutralizing antibodies may prevent infection, they are unlikely to modify outcomes in infected individuals. Broader vaccine approaches targeting multiple HTLV-1 antigens may therefore be required to improve both prevention and clinical management.