A 28-aa pneumococcal surface adhesin A-derived peptide, P4, augments passive immunotherapy and rescues mice from fatal pneumococcal infection

Abstract

Background: P4, a 28-aa peptide derived from pneumococcal surface adhesin A, is a multilineage cell activator in vitro. We hypothesized that P4-mediated activation of phagocytic cells could rapidly and substantially increase opsonophagocytosis of bacteria, which could be translated in vivo to reduced mouse morbidity from fatal pneumococcal infection.

Methods: Reference in vitro opsonophagocytic killing and uptake assays were used with suitable effector cells and pathogen-specific antibodies. P4 peptide solution was added at the preopsonization stage. ND4-SW mice were infected intranasally with Streptococcus pneumoniae serotype 3 (WU2). At 72 and 96 h, infected mice received intraperitoneal or intravenous injection of gamma globulin, followed by an injection of P4.

Results: P4 treatment enhanced in vitro opsonophagocytosis of bacterial pathogens by many fold, and this effect was dependent on complement, P4, and antibody concentrations. Treatment of highly virulent WU2-infected mice with the combination of P4 and serotype-specific antiserum resulted in 100% remission of bacteremia and rescued 80% of the animals (P < .05).

Conclusion: P4 peptide in combination with pathogen-specific antibodies and complement enhances specific opsonophagocytosis and rescues mice from life-threatening pneumococcal infection. P4 peptide provides a fresh direction for therapeutic intervention through augmented passive immunotherapy.