Protection against pneumococcal pneumonia in mice by monoclonal antibodies to pneumolysin.
Pneumolysin (PLY) is an important virulence factor of Streptococcus pneumoniae. We examined the ability of three murine monoclonal antibodies (MAbs) to PLY (PLY-4, PLY-5, and PLY-7) to affect the course of pneumococcal pneumonia in mice. The intravenous administration of antibodies PLY-4 and PLY-7 protected the mice from the lethal effect of the purified toxin. Mice treated with PLY-4 before intranasal inoculation of S. pneumoniae type 2 survived longer (median survival time, 100 h) than did untreated animals (median survival time, 60 h) (P < 0.0001). The median survival time for mice treated with a combination of PLY-4 and PLY-7 was 130 h, significantly longer than that for mice given isotype-matched indifferent MAbs (P = 0.0288) or nontreated mice (P = 0.0002). The median survival time for mice treated with a combination of three MAbs was significantly longer (>480 h) than that for mice treated with PLY-5 (48 h; P < 0.0001), PLY-7 (78 h; P = 0.0007), or PLY-4 (100 h; P = 0.0443) alone. Similarly, the survival rate for mice treated with three MAbs (10 of 20 mice) was significantly higher than the survival rate obtained with PLY-5 (1 of 20; P = 0.0033), PLY-4 (2 of 20; P = 0.0138), or PLY-7 (3 of 20; P = 0.0407) alone. These results suggest that anti-PLY MAbs act with a synergistic effect. Furthermore, MAb administration was associated with a significant decrease in bacterial lung colonization and lower frequencies of bacteremia and tissue injury with respect to the results for the control groups.
Area de Inmunología, Facultad de Medicina, Universidad de Oviedo, Spain. mar@spi.uniovi.es
María del Mar
Mdel M
García-Suárez
María Dolores
MD
Cima-Cabal
Noelia
N
Flórez
Pilar
P
García
Rafael
R
Cernuda-Cernuda
Aurora
A
Astudillo
Fernando
F
Vázquez
Juan R
JR
De los Toyos
F Javier
FJ
Méndez
D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D016470:Bacteremia / Q000401:mortality / Q000517:prevention & control; D001426:Bacterial Proteins; D001769:Blood / Q000382:microbiology; D004357:Drug Synergism; D006801:Humans; D007116:Immunization, Passive; D007275:Injections, Intravenous; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009500:Neutralization Tests; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology; D011018:Pneumonia, Pneumococcal / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D013301:Streptolysins / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae