This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chang, Q.
Right arrow Articles by Pirofski, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chang, Q.
Right arrow Articles by Pirofski, L.

 Previous Article  |  Next Article 

Infection and Immunity, September 2002, p. 4977-4986, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4977-4986.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Structure-Function Relationships for Human Antibodies to Pneumococcal Capsular Polysaccharide from Transgenic Mice with Human Immunoglobulin Loci

Q. Chang,1 Z. Zhong,2 A. Lees,3 M. Pekna,4 and L. Pirofski1,2*

Departments of Microbiology and Immunology,1 Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, New York,2 BioSynexus, Bethesda, Maryland,3 University of Goteborg, Goteborg, Sweden4

Received 18 March 2002/ Returned for modification 14 May 2002/ Accepted 6 June 2002

To investigate the influence of antibody structure and specificity on antibody efficacy against Streptococcus pneumoniae, human monospecific antibodies (MAbs) to serotype 3 pneumococcal capsular polysaccharide (PPS-3) were generated from transgenic mice reconstituted with human immunoglobulin loci (XenoMouse mice) vaccinated with a PPS-3-tetanus toxoid conjugate and their molecular genetic structures, epitope specificities, and protective efficacies in normal and complement-deficient mice were determined. Nucleic acid sequence analysis of three MAbs (A7, 1A2, and 7C5) revealed that they use two different VH3 genes (A7 and 1A2 both use V3-15) and three different V{kappa} gene segments. The MAbs were found to have similar affinities for PPS-3 but different epitope specificities and CDR3 regions. Both A7 and 7C5 had a lysine at the VH-D junction, whereas 1A2 had a threonine. Challenge experiments with serotype 3 S. pneumoniae in BALB/c mice revealed that both 10- and 1-µg doses of A7 and 7C5 were protective, while only a 10-µg dose of 1A2 was protective. Both A7 and 7C5 were also protective in mice lacking either an intact alternative (FB-/-) or classical (C4-/-) complement pathway, but 1A2 was not protective in either strain. Our data suggest that PPS-3 consists of epitopes that can elicit both highly protective and less protective antibodies and that the superior efficacies of certain antibodies may be a function of their structures and/or specificities. Further investigation of relationships between structure, specificity, and efficacy for defined MAbs to PPS may identify antibody features that might be useful surrogates for antibody (and vaccine) efficacy.

* 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.

Editor: J. D. Clements

Infection and Immunity, September 2002, p. 4977-4986, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4977-4986.2002
Copyright © 2002, 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]  
  • Tian, H., Groner, A., Boes, M., Pirofski, L.-a. (2007). Pneumococcal Capsular Polysaccharide Vaccine-Mediated Protection against Serotype 3 Streptococcus pneumoniae in Immunodeficient Mice. Infect. Immun. 75: 1643-1650 [Abstract] [Full Text]  
  • Fabrizio, K., Groner, A., Boes, M., Pirofski, L.-a. (2007). A Human Monoclonal Immunoglobulin M Reduces Bacteremia and Inflammation in a Mouse Model of Systemic Pneumococcal Infection. CVI 14: 382-390 [Abstract] [Full Text]  
  • Kolibab, K., Smithson, S. L., Rabquer, B., Khuder, S., Westerink, M. A. J. (2005). Immune Response to Pneumococcal Polysaccharides 4 and 14 in Elderly and Young Adults: Analysis of the Variable Heavy Chain Repertoire. Infect. Immun. 73: 7465-7476 [Abstract] [Full Text]  
  • Smithson, S. L., Kolibab, K., Shriner, A. K., Srivastava, N., Khuder, S., Westerink, M. A. J. (2005). Immune Response to Pneumococcal Polysaccharides 4 and 14 in Elderly and Young Adults: Analysis of the Variable Light Chain Repertoire. Infect. Immun. 73: 7477-7484 [Abstract] [Full Text]  
  • Burns, T., Abadi, M., Pirofski, L.-a. (2005). Modulation of the Lung Inflammatory Response to Serotype 8 Pneumococcal Infection by a Human Immunoglobulin M Monoclonal Antibody to Serotype 8 Capsular Polysaccharide. Infect. Immun. 73: 4530-4538 [Abstract] [Full Text]  
  • Test, S. T., Mitsuyoshi, J. K., Hu, Y. (2005). Depletion of Complement Has Distinct Effects on the Primary and Secondary Antibody Responses to a Conjugate of Pneumococcal Serotype 14 Capsular Polysaccharide and a T-Cell-Dependent Protein Carrier. Infect. Immun. 73: 277-286 [Abstract] [Full Text]  
  • Buchwald, U. K., Lees, A., Steinitz, M., Pirofski, L.-a. (2005). A Peptide Mimotope of Type 8 Pneumococcal Capsular Polysaccharide Induces a Protective Immune Response in Mice. Infect. Immun. 73: 325-333 [Abstract] [Full Text]  
  • Casadevall, A., Pirofski, L.-a. (2004). New Concepts in Antibody-Mediated Immunity. Infect. Immun. 72: 6191-6196 [Full Text]  
  • Maitta, R. W., Datta, K., Chang, Q., Luo, R. X., Witover, B., Subramaniam, K., Pirofski, L.-a. (2004). Protective and Nonprotective Human Immunoglobulin M Monoclonal Antibodies to Cryptococcus neoformans Glucuronoxylomannan Manifest Different Specificities and Gene Use Profiles. Infect. Immun. 72: 4810-4818 [Abstract] [Full Text]  
  • Dadachova, E., Burns, T., Bryan, R. A., Apostolidis, C., Brechbiel, M. W., Nosanchuk, J. D., Casadevall, A., Pirofski, L. (2004). Feasibility of Radioimmunotherapy of Experimental Pneumococcal Infection. Antimicrob. Agents Chemother. 48: 1624-1629 [Abstract] [Full Text]  
  • Maitta, R. W., Datta, K., Lees, A., Belouski, S. S., Pirofski, L.-a. (2004). Immunogenicity and Efficacy of Cryptococcus neoformans Capsular Polysaccharide Glucuronoxylomannan Peptide Mimotope-Protein Conjugates in Human Immunoglobulin Transgenic Mice. Infect. Immun. 72: 196-208 [Abstract] [Full Text]  
  • Burns, T., Zhong, Z., Steinitz, M., Pirofski, L.-a. (2003). Modulation of Polymorphonuclear Cell Interleukin-8 Secretion by Human Monoclonal Antibodies to Type 8 Pneumococcal Capsular Polysaccharide. Infect. Immun. 71: 6775-6783 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»