Discovery of novel cross-protective Rickettsia prowazekii T-cell antigens using a combined reverse vaccinology and in vivo screening approach.

Abstract

Rickettsial agents are some of the most lethal pathogens known to man. Among them, Rickettsia prowazekii is a select agent with potential use for bioterrorism; yet, there is no anti-Rickettsia vaccine commercially available. Owing to the obligate intracellular lifestyle of rickettsiae, CD8(+) T cells are indispensable for protective cellular immunity. Furthermore, T cells can mediate cross-protective immunity between different pathogenic Rickettsia, a finding consistent with the remarkable similarity among rickettsial genomes. However, Rickettsia T cell antigens remain unidentified. In the present study, we report an algorithm that allowed us to identify and validate four novel R. prowazekii vaccine antigen candidates recognized by CD8(+) T cells from a set of twelve in silico-defined protein targets. Our results highlight the importance of combining proteasome-processing as well as MHC class-I-binding predictions. The novel rickettsial vaccine candidate antigens, RP778, RP739, RP598, and RP403, protected mice against a lethal challenge with Rickettsia typhi, which is indicative of cross-protective immunity within the typhus group rickettsiae. Together, our findings validate a reverse vaccinology approach as a viable strategy to identify protective rickettsial antigens and highlight the feasibility of a subunit vaccine that triggers T-cell-mediated cross-protection among diverse rickettsiae.

• Authors: Erika Caro-Gomez, Michal Gazi, Yenny Goez, Gustavo Valbuena
• Journal: Vaccine (Vaccine) Vol. 32 Issue 39 Pg. 4968-76 (Sep 03 2014) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 25010827 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Antigens, Bacterial
• Histocompatibility Antigens Class I
• Rickettsial Vaccines

Topics

• Algorithms
• Animals
• Antigens, Bacterial (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cross Protection
• Histocompatibility Antigens Class I (immunology)
• Mice
• Rickettsia prowazekii (immunology)
• Rickettsial Vaccines (immunology)