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Infection and Immunity, April 2009, p. 1502-1513, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01075-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Efficacy of Opsonic and Nonopsonic Serotype 3 Pneumococcal Capsular Polysaccharide-Specific Monoclonal Antibodies against Intranasal Challenge with Streptococcus pneumoniae in Mice{triangledown}

Haijun Tian,1 Sarah Weber,2 Peter Thorkildson,3 Thomas R. Kozel,3 and Liise-anne Pirofski1,2*

Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center,1 Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461,2 Department of Microbiology and Immunology/320, University of Nevada School of Medicine, Reno, Nevada 895573

Received 28 August 2008/ Returned for modification 22 October 2008/ Accepted 7 January 2009

Serotype-specific antibodies to pneumococcal capsular polysaccharide (PPS) are a critical component of vaccine-mediated immunity to Streptococcus pneumoniae. In this study, we investigated the in vitro opsonophagocytic activities of three PPS-specific mouse immunoglobulin G1 monoclonal antibodies (MAbs), 1E2, 5F6, and 7A9, and determined their in vivo efficacies against intranasal challenge with WU2, a serotype 3 pneumococcal strain, in normal and immunodeficient mice. The MAbs had different in vitro activities in a pneumococcal killing assay: 7A9 enhanced killing by mouse neutrophils and J774 cells in the presence of a complement source, whereas 5F6 promoted killing in the absence, but not the presence, of complement, and 1E2 did not promote killing under any conditions. Nonetheless, all three MAbs protected normal and complement component 3-deficient mice from a lethal intranasal challenge with WU2 in passive-immunization experiments in which 10 µg of the MAbs were administered intraperitoneally before intranasal challenge. In contrast, only 1E2 protected Fc{gamma} receptor IIB knockout (Fc{gamma}RIIB KO) mice and mice that were depleted of neutrophils with the MAb RB6, whereas 7A9 and 5F6 required neutrophils and Fc{gamma}RIIB to mediate protection. Conversely, 7A9 and 5F6 protected Fc{gamma}R KO mice, but 1E2 did not. Hence, the efficacy of 1E2 required an activating Fc{gamma}R(s), whereas 5F6 and 7A9 required the inhibitory Fc{gamma}R (Fc{gamma}RIIB). Taken together, our data demonstrate that both MAbs that do and do not promote pneumococcal killing in vitro can mediate protection in vivo, although their efficacies depend on different host receptors and/or components.

* Corresponding author. Mailing address: Division of Infectious Diseases, Albert Einstein College of Medicine, Room 709 Forchheimer Bldg., 1300 Morris Park Avenue, Bronx, NY 10461. Phone: (718) 430-2372. Fax: (718) 430-2292. E-mail: pirofski{at}aecom.yu.edu

{triangledown} Published ahead of print on 21 January 2009.

Editor: A. Camilli

Infection and Immunity, April 2009, p. 1502-1513, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01075-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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