PD-1 blockade in rhesus macaques: impact on chronic infection and prophylactic vaccination

Area of Science:

• Immunology
• Virology
• Oncology

Background:

• Programmed Cell Death 1 (PD-1) is a key immune checkpoint receptor.
• PD-1 signaling down-regulates immune responses, facilitating immune evasion by tumors and chronic viruses.
• Blocking PD-1 may restore or enhance host immune functions.

Purpose of the Study:

• To investigate the therapeutic and prophylactic potential of blocking the PD-1 pathway.
• To evaluate anti-PD-1 monoclonal antibodies (mAbs) in nonhuman primate models.

Main Methods:

• Generated mAbs targeting human PD-1 and assessed their in vitro binding and blocking capabilities.
• Tested functional T cell responses in vitro.
• Evaluated a lead anti-PD-1 mAb candidate in two in vivo rhesus macaque models: therapeutic (SIV infection) and prophylactic (SIV-gag vaccination).

Main Results:

• In SIV-infected macaques, anti-PD-1 mAb treatment led to transient viral load increases followed by a return to baseline or lower levels.
• In naive macaques vaccinated with an SIV-gag adenovirus vector, PD-1 blockade significantly increased the peak percentage of Gag epitope-specific T cells.
• Results demonstrate PD-1 blockade's efficacy in modulating immune responses in vivo.

Conclusions:

• PD-1 blockade can enhance immune responses in both therapeutic and prophylactic settings.
• Nonhuman primate studies support a broader role for PD-1 in immune modulation.
• Findings suggest potential applications of PD-1 blockade in human immunotherapy.