Regions of PspA/EF3296 best able to elicit protection against Streptococcus pneumoniae in a murine infection model
Roche, Hazeline ; Håkansson, Anders P LU
; Hollingshead, Susan K
and Briles, David E
(2003)
In Infection and Immunity
71(3).
p.41-1033
- Abstract
Pneumococcal surface protein A (PspA) can elicit protection against Streptococcus pneumoniae in mouse infection models. PspA is classified by serology and amino acid sequence into two major families that are divided by sequence into five clades. The most variable portion of the molecule is the alpha-helical domain, which comprises the N-terminal half of PspA. Prior studies of a family 1 PspA protein observed that protective antibodies are reactive with epitopes in the alpha-helical domain and that most cross-protective epitopes mapped to the 108 most C-terminal amino acids of the alpha-helical region. In these studies, we have used six overlapping recombinant fragments of family 2, clade 3 PspA/EF3296 to map the protection-eliciting... (More)
Pneumococcal surface protein A (PspA) can elicit protection against Streptococcus pneumoniae in mouse infection models. PspA is classified by serology and amino acid sequence into two major families that are divided by sequence into five clades. The most variable portion of the molecule is the alpha-helical domain, which comprises the N-terminal half of PspA. Prior studies of a family 1 PspA protein observed that protective antibodies are reactive with epitopes in the alpha-helical domain and that most cross-protective epitopes mapped to the 108 most C-terminal amino acids of the alpha-helical region. In these studies, we have used six overlapping recombinant fragments of family 2, clade 3 PspA/EF3296 to map the protection-eliciting regions of its alpha-helical domain. The three fragments, which included the 104 most C-terminal amino acids of the alpha-helical domain (314 to 418), could each elicit protection against EF3296. A fragment comprising amino acids 75 to 305 failed to elicit significant protection. A fragment containing amino acids 1 to 115 elicited protection against EF3296 in BALB/c mice but not in CBA/N mice. All three fragments containing amino acids 314 to 418 were able to elicit cross-protection against pneumococci expressing PspA proteins of clades 2, 3, 4, and 5. Cross-protection elicited by these three fragments was easier to demonstrate in CBA/N mice than in BALB/c mice. The 1-to-115 fragment, however, elicited some cross-protection against clades 2 and 4 in BALB/c mice but not in CBA/N mice. These studies provide support for the importance of the C-terminal 104 and N-terminal 115 amino acids of the alpha-helical region of PspA in the elicitation of cross-protection.
(Less)
- author
- Roche, Hazeline
; Håkansson, Anders P
LU
; Hollingshead, Susan K
and Briles, David E
- publishing date
- 2003-03
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Antibodies, Bacterial, Bacterial Proteins, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Epitope Mapping, Immunization, Mice, Mice, Inbred BALB C, Mice, Inbred CBA, Peptide Fragments, Pneumococcal Infections, Recombinant Proteins, Species Specificity, Streptococcus pneumoniae, Structure-Activity Relationship
- in
- Infection and Immunity
- volume
- 71
- issue
- 3
- pages
- 9 pages
- publisher
- American Society for Microbiology
- external identifiers
-
- pmid:12595413
- scopus:0037369739
- ISSN
- 0019-9567
- DOI
- 10.1128/IAI.71.3.1033-1041.2003
- language
- English
- LU publication?
- no
- id
- c8b9dd7f-8cd5-4db0-82fb-cea1259805fb
- date added to LUP
- 2016-05-21 11:52:45
- date last changed
- 2024-04-04 20:40:10
@article{c8b9dd7f-8cd5-4db0-82fb-cea1259805fb,
abstract = {{<p>Pneumococcal surface protein A (PspA) can elicit protection against Streptococcus pneumoniae in mouse infection models. PspA is classified by serology and amino acid sequence into two major families that are divided by sequence into five clades. The most variable portion of the molecule is the alpha-helical domain, which comprises the N-terminal half of PspA. Prior studies of a family 1 PspA protein observed that protective antibodies are reactive with epitopes in the alpha-helical domain and that most cross-protective epitopes mapped to the 108 most C-terminal amino acids of the alpha-helical region. In these studies, we have used six overlapping recombinant fragments of family 2, clade 3 PspA/EF3296 to map the protection-eliciting regions of its alpha-helical domain. The three fragments, which included the 104 most C-terminal amino acids of the alpha-helical domain (314 to 418), could each elicit protection against EF3296. A fragment comprising amino acids 75 to 305 failed to elicit significant protection. A fragment containing amino acids 1 to 115 elicited protection against EF3296 in BALB/c mice but not in CBA/N mice. All three fragments containing amino acids 314 to 418 were able to elicit cross-protection against pneumococci expressing PspA proteins of clades 2, 3, 4, and 5. Cross-protection elicited by these three fragments was easier to demonstrate in CBA/N mice than in BALB/c mice. The 1-to-115 fragment, however, elicited some cross-protection against clades 2 and 4 in BALB/c mice but not in CBA/N mice. These studies provide support for the importance of the C-terminal 104 and N-terminal 115 amino acids of the alpha-helical region of PspA in the elicitation of cross-protection.</p>}},
author = {{Roche, Hazeline and Håkansson, Anders P and Hollingshead, Susan K and Briles, David E}},
issn = {{0019-9567}},
keywords = {{Animals; Antibodies, Bacterial; Bacterial Proteins; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Immunization; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Peptide Fragments; Pneumococcal Infections; Recombinant Proteins; Species Specificity; Streptococcus pneumoniae; Structure-Activity Relationship}},
language = {{eng}},
number = {{3}},
pages = {{41--1033}},
publisher = {{American Society for Microbiology}},
series = {{Infection and Immunity}},
title = {{Regions of PspA/EF3296 best able to elicit protection against Streptococcus pneumoniae in a murine infection model}},
url = {{http://dx.doi.org/10.1128/IAI.71.3.1033-1041.2003}},
doi = {{10.1128/IAI.71.3.1033-1041.2003}},
volume = {{71}},
year = {{2003}},
}