Protection against pneumococcal infection elicited by immunization with multiple pneumococcal heat shock proteins.

Abstract

Heat shock proteins (HSPs) play important roles in the pathogenesis of pneumococcal infection, and they are considered as potential protein vaccine antigens. In this study, we investigated the efficacy of immunization with pneumococcal HSPs, including ClpP (hsp100/Clp peptidase subunit), DnaJ (hsp40) and GroEL (hsp60), to protect against pneumococcal carriage, lung colonization and sepsis in mouse models using different serotypes of Streptococcus pneumoniae. In a nasopharyngeal colonization model by serotype 6B or 14 and in a lung colonization model by serotype 19F, immunization with pneumococcal HSPs could elicit effective protection. Likewise, vaccination with ClpP, DnaJ or GroEL allowed significantly longer mouse survival times after lethal intranasal challenge with serotype pneumococcal 2, 3 or 4. Interestingly, combinations of these HSPs could consistently enhance the protection against nasopharynx carriage, lung colonization as well as invasive infection caused by different pneumococcal serotypes. In an in vitro killing assay, anti-sera against ClpP, DnaJ or GroEL could kill S. pneumoniae by polymorphonuclear leukocytes in a complement-dependent way, and combinations of multiple anti-sera against these HSPs could increase the killing ability compared with single anti-sera. Finally, passive immunization studies with anti-sera against pneumococcal HSPs also demonstrated that an additive effect could be achieved by using multiple anti-sera when compared with single anti-sera. Thus, inclusion of multiple pneumococcal HSPs is important for the development of protein-based pneumococcal vaccines.

• Authors: Ju Cao, Xiaojiao Zhang, Yi Gong, Yuhong Zhang, Yali Cui, Xiaofei Lai, Yibing Yin, Meijuan Li, Dairong Li, Liping Zhang
• Journal: Vaccine (Vaccine) Vol. 31 Issue 35 Pg. 3564-71 (Aug 02 2013) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 23727004 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Antibodies, Bacterial
• Bacterial Proteins
• Chaperonin 60
• HSP40 Heat-Shock Proteins
• Heat-Shock Proteins
• Pneumococcal Vaccines
• Serine Endopeptidases
• ClpP protein, Streptococcus pneumoniae
• Endopeptidase Clp

Topics

• Administration, Intranasal
• Animals
• Antibodies, Bacterial (blood)
• Bacterial Load (immunology)
• Bacterial Proteins (immunology)
• Chaperonin 60 (immunology)
• Endopeptidase Clp
• HSP40 Heat-Shock Proteins (immunology)
• Heat-Shock Proteins (administration & dosage, immunology)
• Immunization, Passive
• Lung (immunology, microbiology)
• Mice
• Mice, Inbred BALB C
• Nasopharyngeal Diseases (immunology, prevention & control)
• Pneumococcal Vaccines (immunology)
• Pneumonia, Pneumococcal (immunology, prevention & control)
• Serine Endopeptidases (immunology)
• Streptococcus pneumoniae (immunology)
• Vaccination