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 Hou, V. C.
Right arrow Articles by Granoff, D. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hou, V. C.
Right arrow Articles by Granoff, D. M.

 Previous Article  |  Next Article 

Infection and Immunity, December 2003, p. 6844-6849, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6844-6849.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Conformational Epitopes Recognized by Protective Anti-Neisserial Surface Protein A Antibodies

Victor C. Hou, Gregory R. Moe, Zyde Raad, Tomi Wuorimaa, and Dan M. Granoff*

Children's Hospital Oakland Research Institute, Oakland, California

Received 30 June 2003/ Returned for modification 6 August 2003/ Accepted 3 September 2003

NspA is a conserved membrane protein that elicits protective antibody responses in mice against Neisseria meningitidis. A recent crystallographic study showed that NspA adopts an eight-stranded ß-barrel structure when reconstituted in detergent. In order to define the segments of NspA-containing epitopes recognized by protective murine anti-NspA antibodies, we studied the binding of two bactericidal and protective anti-NspA monoclonal antibodies (MAbs), AL12 and 14C7. Neither MAb binds to overlapping synthetic peptides (10-mers, 12-mers, and cyclic 12-mers) corresponding to the entire mature sequence of NspA, or to denatured recombinant NspA (rNspA), although binding to the protein can be restored by refolding in liposomes. Based on the ability of the two MAbs to bind to Escherichia coli microvesicles prepared from a set of rNspA variants created by site-specific mutagenesis, the most important contacts between the MAbs and NspA appear to be located within the LGG segment of loop 3. The conformation of loop 2 also appears to be an important determinant, as particular combinations of residues in this segment resulted in loss of antibody binding. Thus, the two anti-NspA MAbs recognize discontinuous conformational epitopes that result from the close proximity of loops 2 and 3 in the three-dimensional structure of NspA. The data suggest that optimally immunogenic vaccines using rNspA will require formulations that permit proper folding of the protein.

* Corresponding author. Mailing address: 5700 Martin Luther King Jr. Way, Oakland, CA 94609. Phone: (510) 450-7640. Fax: (510) 450-7915. E-mail: dgranoff{at}chori.org.

Editor: F. C. Fang

Infection and Immunity, December 2003, p. 6844-6849, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6844-6849.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • de Filippis, I. (2009). Quest for a broad-range vaccine against Neisseria meningitidis serogroup B: implications of genetic variations of the surface-exposed proteins. J Med Microbiol 58: 1127-1132 [Abstract] [Full Text]  
  • Norheim, G., Aseffa, A., Yassin, M. A., Mengistu, G., Kassu, A., Fikremariam, D., Tamire, W., Merid, Y., Hoiby, E. A., Caugant, D. A., Fritzsonn, E., Tangen, T., Melak, B., Berhanu, D., Harboe, M., Kolberg, J., Rosenqvist, E. (2008). Specificity of Subcapsular Antibody Responses in Ethiopian Patients following Disease Caused by Serogroup A Meningococci. CVI 15: 863-871 [Abstract] [Full Text]  
  • Turner, D. P. J., Marietou, A. G., Johnston, L., Ho, K. K. L., Rogers, A. J., Wooldridge, K. G., Ala'Aldeen, D. A. A. (2006). Characterization of MspA, an Immunogenic Autotransporter Protein That Mediates Adhesion to Epithelial and Endothelial Cells in Neisseria meningitidis.. Infect. Immun. 74: 2957-2964 [Abstract] [Full Text]  
  • Giersing, B., Miura, K., Shimp, R., Wang, J., Zhou, H., Orcutt, A., Stowers, A., Saul, A., Miller, L. H., Long, C., Singh, S. (2005). Posttranslational Modification of Recombinant Plasmodium falciparum Apical Membrane Antigen 1: Impact on Functional Immune Responses to a Malaria Vaccine Candidate. Infect. Immun. 73: 3963-3970 [Abstract] [Full Text]  
  • O'Dwyer, C. A., Reddin, K., Martin, D., Taylor, S. C., Gorringe, A. R., Hudson, M. J., Brodeur, B. R., Langford, P. R., Kroll, J. S. (2004). Expression of Heterologous Antigens in Commensal Neisseria spp.: Preservation of Conformational Epitopes with Vaccine Potential. Infect. Immun. 72: 6511-6518 [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»