Time dependence of protective post-exposure prophylaxis with human monoclonal antibodies against pathogenic SHIV...

Area of Science:

• Virology
• Immunology
• Primate Models

Background:

• Postnatal simian-human immunodeficiency virus (SHIV) transmission is a critical concern.
• Previous studies demonstrated sterilizing protection with 1-hour post-exposure prophylaxis (PEP) using neutralizing monoclonal antibodies (nmAbs).

Purpose of the Study:

• To evaluate the efficacy of nmAbs as passive immunoprophylaxis at later time points (12 and 24 hours) post-exposure in a primate model.
• To determine the potential and limitations of nmAbs in preventing SHIV infection and disease in neonates.

Main Methods:

• Utilized a primate model of postnatal SHIV transmission.
• Administered a triple combination of nmAbs at 1, 12, and 24 hours post-oral SHIV challenge to neonatal macaques.
• Assessed protection against infection, viremia, and acute disease.

Main Results:

• Passive immunoprophylaxis with nmAbs at 12 and 24 hours post-exposure partially protected against SHIV infection or disease.
• While 24-hour PEP did not achieve sterilizing immunity, it effectively contained viremia and prevented acute illness.
• Efficacy was dependent on nmAb potency, dose, and the time window between exposure and immunotherapy initiation.

Conclusions:

• Passive immunotherapy with nmAbs demonstrates partial protective capacity against SHIV even when initiated later post-exposure.
• The timing of immunotherapy administration is a critical factor influencing the success of passive immunization against viral transmission.
• Further research into optimizing nmAb potency, dosage, and treatment windows is warranted for effective passive immunoprophylaxis strategies.