Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Antiretroviral therapy (ART) as pre-exposure prophylaxis (PrEP) is crucial for HIV prevention but faces challenges like adherence and resistance.
• Developing effective prophylactic strategies is essential to curb the HIV epidemic.

Purpose of the Study:

• To evaluate the efficacy of Leronlimab, a CCR5-specific antibody, in preventing HIV acquisition in a non-human primate model.
• To assess the impact of Leronlimab dosage and administration frequency on protection against CCR5-tropic SHIV infection.

Main Methods:

• Rhesus macaques were challenged intrarectally with CCR5-tropic SHIV_SF162P3.
• Animals received weekly injections of Leronlimab at 10 mg/kg or biweekly injections at 50 mg/kg.
• Protection was assessed by viral load monitoring and analysis of CCR5 receptor occupancy in tissue biopsies.
• Long-term outcomes and potential for viral transmission via cell transfer were evaluated after drug washout.

Main Results:

• Weekly Leronlimab (10 mg/kg) provided partial protection, while biweekly Leronlimab (50 mg/kg) conferred complete protection against SHIV acquisition.
• Protected macaques showed full CCR5 receptor occupancy and no detectable viral nucleic acids in tissue biopsies post-challenge.
• Protected animals remained aviremic after Leronlimab washout, and hematologic cell transfer did not transmit infection.

Conclusions:

• CCR5 blockade using Leronlimab is a viable and promising approach for HIV pre-exposure prophylaxis.
• These findings support the initiation of clinical trials to investigate Leronlimab for human HIV prevention.