Delayed viral rebound post-ART interruption in infant macaques given SIV-specific neutralizing antibodies.

Area of Science:

• Immunology
• Virology
• Preclinical Research

Background:

• Antiretroviral therapy (ART) is standard for HIV management, but viral rebound occurs upon cessation.
• Novel strategies are crucial to prevent viral rebound and achieve long-term remission without continuous ART.
• Monoclonal antibodies (mAbs) show promise as an intervention for post-ART viral control.

Purpose of the Study:

• To evaluate the efficacy of simian immunodeficiency virus (SIV) Env-specific rhesus monoclonal antibodies (RhmAbs) in delaying viral rebound in a pediatric HIV model.
• To investigate the correlation between RhmAb concentrations, anti-drug antibodies, and viral rebound kinetics.
• To assess the impact of RhmAb treatment on T cell responses and viral neutralization capacity.

Main Methods:

• A pediatric HIV model using rhesus macaques was employed.
• RhmAbs targeting SIV Env were administered prior to antiretroviral therapy (ART) cessation.
• Viral load, RhmAb concentrations, anti-drug antibodies, SIVgag-specific CD8+ T cell responses, and neutralization breadth/potency were measured.

Main Results:

• RhmAb treatment significantly delayed viral rebound compared to controls (median 64 vs. 7.5 days).
• Time to rebound strongly correlated with RhmAb concentrations and anti-drug antibody levels.
• RhmAb administration increased SIVgag-specific CD8+ T cell responses and expanded neutralization breadth against tier 2 and tier 3 viruses.

Conclusions:

• SIV Env RhmAbs administered before ART cessation prolong time to viral rebound in a pediatric HIV model.
• RhmAbs enhance antiviral T cell responses and broaden neutralization capacity.
• Neutralizing antibodies represent a viable strategy to promote post-ART viral control.