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


CONCLUSIONS
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.
Rajam
Gowrisankar
G
Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Skinner
Julie
J
Melnick
Nikkol
N
Martinez
Joseph
J
Carlone
George M
GM
Sampson
Jacquelyn S
JS
Ades
Edwin W
EW
D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry*; D007116:Immunization, Passive; D051379:Mice; D009504:Neutrophils; D010587:Phagocytosis / Q000502:physiology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000628:therapy; D013296:Streptococcus pneumoniae / Q000276:immunology*; D005719:gamma-Globulins / Q000276:immunology
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D005719:gamma-Globulins; C051592:pneumococcal surface protein A