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Clinical and Vaccine Immunology, April 2007, p. 382-390, Vol. 14, No. 4
1071-412X/07/$08.00+0     doi:10.1128/CVI.00374-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Human Monoclonal Immunoglobulin M Reduces Bacteremia and Inflammation in a Mouse Model of Systemic Pneumococcal Infection{triangledown}

Kevin Fabrizio,1 Abraham Groner,3 Marianne Boes,2 and Liise-anne Pirofski1,3*

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461,1 Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115,2 Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York3

Received 9 October 2006/ Returned for modification 13 November 2006/ Accepted 5 February 2007

Antibody-based approaches to pneumococcal disease may hold promise for immunocompromised patients in whom vaccines are less immunogenic and/or in the context of antimicrobial resistance. Antibody-mediated protection against experimental pneumococcal pneumonia has been shown to depend on immunoregulation, but the relationship between antibody and protection against pneumococcal sepsis and immunoregulation has not been examined. Similarly, the requirement for B and T cells for antibody efficacy is not known. In this study, we determined the efficacy of the human pneumococcal capsular polysaccharide serotype 3-specific antibody, A7 (immunoglobulin M [IgM]), in secretory IgM (sIgM)–/–, CD4–/–, CD8–/–, µMT–/–, and SCID mice and investigated its effect on cytokine and chemokine expression in sera and spleens from mice with intact cellular immunity. A7 is known to be protective against systemic infection with serotype 3 and to require complement for efficacy. Compared to that of an isotype control antibody, A7 administration prolonged the survival of mice of each immunodeficient strain and was associated with a significant reduction in CFU in blood, lung, and spleen samples and a significantly reduced level of keratinocyte-derived chemokine (KC), interleukin-6 (IL-6), and macrophage inflammatory protein-2 (MIP-2) expression in normal and sIgM–/– mice. Studies with mice treated with penicillin revealed similar reductions in CFU and similar levels of IL-6, KC, or MIP-2 expression in A7- and penicillin-treated mice. These findings demonstrate that natural IgM and B and T cells are dispensable for A7-mediated protection against experimental pneumococcal sepsis and suggest that the efficacy of antibody-mediated protection depends on immunomodulation. Taken together, our data extend the association between antibody-mediated protection and immunomodulation to protection against systemic pneumococcal infection and to a clinically important serotype often responsible for pneumococcal sepsis.

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

{triangledown} Published ahead of print on 14 February 2007.

Clinical and Vaccine Immunology, April 2007, p. 382-390, Vol. 14, No. 4
1071-412X/07/$08.00+0     doi:10.1128/CVI.00374-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tian, H., Weber, S., Thorkildson, P., Kozel, T. R., Pirofski, L.-a. (2009). Efficacy of Opsonic and Nonopsonic Serotype 3 Pneumococcal Capsular Polysaccharide-Specific Monoclonal Antibodies against Intranasal Challenge with Streptococcus pneumoniae in Mice. Infect. Immun. 77: 1502-1513 [Abstract] [Full Text]  


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