Targeted Immuno-Antiretroviral to Promote Dual Protection against HIV: A Proof-of-Concept Study

Area of Science:

• Immunology
• Nanotechnology
• Virology

Background:

• C-C motif chemokine receptor-5 (CCR5) on T-cells is crucial for HIV infection and latency.
• Antiretrovirals (ARVs) effectively suppress but do not eradicate HIV.
• Targeting CCR5+ T-cells presents a strategy to enhance HIV prevention and treatment.

Purpose of the Study:

• To design and evaluate a novel nanoformulation for targeted delivery of ARVs to CCR5-expressing T-cells.
• To investigate the dual-action mechanism of CCR5-blocking and ARV delivery for HIV prevention.
• To assess the potential of this nanoformulation in achieving a functional cure for HIV/AIDS.

Main Methods:

• Surface conjugation of nanoformulation with anti-CCR5 monoclonal antibodies (CCR5 mAb).
• Loading of nanoformulation with dolutegravir+tenofovir alafenamide (D+T) ARVs.
• In vitro assessment of binding affinity to CCR5+ cells and in vivo pre-exposure prophylaxis study.

Main Results:

• Targeted nanoformulation showed enhanced CCR5 binding affinity and prolonged ARV intracellular retention.
• Demonstrated high binding to CCR5+ CD4+ T-cells, monocytes, and other relevant immune cells.
• Pre-exposure prophylaxis study indicated a "protective immune phenotype" with boosted T-helper, temporary memory, and effector cells.

Conclusions:

• The developed ARV-loaded nanoformulation effectively targets CCR5+ T-cells.
• This dual-action strategy of CCR5 blockade and targeted ARV delivery shows promise for HIV prevention.
• The findings support the potential of this nanoformulation as a multifactorial solution towards an HIV functional cure.