Mapping of Epitopes Recognized by Antibodies Induced by Immunization of Mice with PspA and PspC

Vadesilho, C. F. M., Ferreira, Daniela ORCID: https://orcid.org/0000-0002-0594-0902, Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116, Briles, D. E., Moreno, A. T., Oliveira, M. L. S., Ho, P. L. and Miyaji, E. N. (2014) 'Mapping of Epitopes Recognized by Antibodies Induced by Immunization of Mice with PspA and PspC'. Clinical and Vaccine Immunology, Vol 21, Issue 7, pp. 940-948.

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Abstract

Pneumococcal surface protein A (PspA) and pneumococcal surface protein C (PspC) are important candidates for an alternative vaccine against pneumococcal infections. Since these antigens show variability, the use of variants that do not afford broad protection may lead to the selection of vaccine escape bacteria. Epitopes capable of inducing antibodies with broad cross-reactivities should thus be the preferred antigens. In this work, experiments using peptide arrays show that most linear epitopes recognized by antibodies induced in mice against different PspAs were located at the initial 44 amino acids of the mature protein and that antibodies against these linear epitopes did not confer protection against a lethal challenge. Conversely, linear epitopes recognized by antibodies to PspC included the consensus sequences involved in the interaction with human factor H and secretory immunoglobulin A (sIgA). Since linear epitopes of PspA were not protective, larger overlapping fragments containing 100 amino acids of PspA of strain Rx1 were constructed (fragments 1 to 7, numbered from the N terminus) to permit the mapping of antibodies with conformational epitopes not represented in the peptide arrays. Antibodies from mice immunized with fragments 1, 2, 4, and 5 were capable of binding onto the surface of pneumococci and mediating protection against a lethal challenge. The fact that immunization of mice with 100-amino-acid fragments located at the more conserved N-terminal region of PspA (fragments 1 and 2) induced protection against a pneumococcal challenge indicates that the induction of antibodies against conformational epitopes present at this region may be important in strategies for inducing broad protection against pneumococci.

Item Type:	Article
Subjects:	QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 805 Vaccines. Antitoxins. Toxoids WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1128/CVI.00239-14
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	02 Jun 2015 10:37
Last Modified:	05 Nov 2019 14:56
URI:	https://archive.lstmed.ac.uk/id/eprint/5178

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