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

Author(s)

Vadesilho, Cintia F. M. ^[1] ; Ferreira, Daniela M. ^[2] ; Gordon, Stephen B. ^[2] ; Briles, David E. ^[3] ; Moreno, Adriana T. ^[1] ; Oliveira, Maria Leonor S. ^[1] ; Ho, Paulo L. ^[1] ; Miyaji, Eliane N. ^[1]

Affiliation

^[1] Inst Butantan, Ctr Biotecnol, Sao Paulo - Brazil

^[2] Univ Liverpool, Liverpool Sch Trop Med, Resp Infect Grp, Liverpool L3 5QA, Merseyside - England

^[3] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL - USA

• Document type: Journal article
• Source: Clinical and Vaccine Immunology; v. 21, n. 7, p. 940-948, JUL 2014.
• Web of Science Citations: 11

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. (AU)

• FAPESP's process: 11/13671-5 - Mapping of epitopes present in variants of the Streptococcus pneumoniae vaccine antigens PspA (Pneumococcal surface protein A) and PspC (Pneumococcal surface protein C)
• Grantee: Cintia Fiuza Marques Vadesilho
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/50816-4 - Multi-peptide vaccine to confer serotype-independent protection against pneumonia
• Grantee: Eliane Namie Miyaji
• Support Opportunities: Regular Research Grants