Regions of PspA/EF3296 Best Able To Elicit Protection against Streptococcus pneumoniae in a Murine Infection Model

AUTOR(ES)

Roche, Hazeline

FONTE

American Society for Microbiology

RESUMO

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 α-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 α-helical domain and that most cross-protective epitopes mapped to the 108 most C-terminal amino acids of the α-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 α-helical domain. The three fragments, which included the 104 most C-terminal amino acids of the α-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 α-helical region of PspA in the elicitation of cross-protection.

Documentos Relacionados

• Comparison of the PspA Sequence from Streptococcus pneumoniae EF5668 to the Previously Identified PspA Sequence from Strain Rx1 and Ability of PspA from EF5668 To Elicit Protection against Pneumococci of Different Capsular Types
• Pharmacodynamic Assessment of Ertapenem (MK-0826) against Streptococcus pneumoniae in a Murine Neutropenic Thigh Infection Model
• Oral immunization with PspA elicits protective humoral immunity against Streptococcus pneumoniae infection.
• Characterization of an antigen from Leishmania amazonensis amastigotes able to elicit protective responses in a murine model.
• Influence of Macrolide Susceptibility on Efficacies of Clarithromycin and Azithromycin against Streptococcus pneumoniae in a Murine Lung Infection Model