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Infection and Immunity, August 2004, p. 4534-4540, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4534-4540.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Protection against Pneumococcal Pneumonia in Mice by Monoclonal Antibodies to Pneumolysin

María del Mar García-Suárez,1* María Dolores Cima-Cabal,2 Noelia Flórez,2 Pilar García,2 Rafael Cernuda-Cernuda,3 Aurora Astudillo,4 Fernando Vázquez,2 Juan R. De Los Toyos,1 and F. Javier Méndez2

Área de Inmunología,1 Área de Microbiología,2 Área de Biología Celular, Facultad de Medicina, Universidad de Oviedo,3 Servicio de Anatomía Patológica, Hospital Central de Asturias, 33006 Oviedo, Spain4

Received 11 March 2004/ Returned for modification 15 April 2004/ Accepted 3 May 2004

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.

* Corresponding author. Mailing address: Área de Inmunología, Facultad de Medicina, c/ Julián Clavería s/n, 33006 Oviedo, Spain. Phone: 34 985 10 27 40. Fax: 34 985 10 31 48. E-mail: mar{at}spi.uniovi.es.

Editor: J. N. Weiser

Infection and Immunity, August 2004, p. 4534-4540, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4534-4540.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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