Common Acquisition of Broadly Neutralizing Antibodies in an HTLV-1c+ First Nations Cohort from Central Australia

Grimley, SL; Monard, SC; Hirons, A; Yap, AHY; Collins, S; Yurick, D; Khoury, G; Ellenberg, PC; Pellegrini, M; Einsiedel, LJ; Purcell, DFJ

Author(s): Grimley, SL; Monard, SC; Hirons, A; Yap, AHY; Collins, S; Yurick, D; Khoury, G; Ellenberg, PC; Pellegrini, M; Einsiedel, LJ; Purcell, DFJ;
Details: Publication Year 2026-03-24,Volume 18,Issue #4,Page 402
Journal Title: Viruses
Abstract: Human T-cell leukemia virus type-1 (HTLV-1) is endemic to numerous regions worldwide, including Central Australia. The Australo-Melanesian subtype-C is endemic within Australia and Oceania, whereas subtype-A is the most widely distributed subtype globally. The lack of an approved vaccine highlights HTLV-1 as a neglected public health issue. To inform the development of HTLV-1 Envelope (Env)-based vaccines, we assessed anti-Env antibodies in an HTLV-1c+ cohort of First Nations individuals in Central Australia. Of the 62 plasma samples from patients with confirmed HTLV-1 serological diagnosis, 76% were positive for Env binding in ELISA, but 90% neutralized HTLV-1c pseudovirus (PSV) infection. Neutralization breadth with the capability of blocking both subtype-A and subtype-C PSV infection was identified in 100% of samples tested. Proviral load was positively associated with anti-Env response, with binding epitopes mapping to the proline-rich region of gp46-SU. Env-directed IgG showed the capacity to engage Fcγ receptors key to inducing antibody-dependent cellular cytotoxicity/phagocytosis responses. Serological response was not associated with comorbidities linked to HTLV-1c in this population (bronchiectasis, chronic kidney disease, diabetes). These findings demonstrate that potent humoral immunity arises and is sustained during HTLV-1 infection, suggesting that an Env-based vaccine displaying authentically native epitopes will be capable of recapitulating these neutralizing responses.
Publisher: MDPI
Keywords: Humans; *Human T-lymphotropic virus 1/immunology; *HTLV-I Infections/immunology/epidemiology/virology; Australia/epidemiology; Female; Male; Adult; Middle Aged; Cohort Studies; *Broadly Neutralizing Antibodies/immunology/blood; *Antibodies, Neutralizing/immunology/blood; *Antibodies, Viral/immunology/blood; *HTLV-I Antibodies/blood/immunology; Immunoglobulin G/immunology/blood; Epitopes/immunology; Aged; Envelope; Htlv-1; neutralizing antibodies; proviral load; seroprevalence
Research Division(s): Infection and Global Health
PubMed ID: 42043191
Publisher's Version: https://doi.org/10.3390/v18040402
Open Access at Publisher's Site: https://doi.org/10.3390/v18040402
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-05-07 08:23:26

Last Modified: 2026-05-07 08:25:05