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Title: Genome-wide screening and identification of antigens for rickettsial vaccine development

item PALMER, G - Washington State University
item BROWN, W - Washington State University
item Noh, Susan
item BRAYTON, K - Washington State University

Submitted to: FEMS Immunology and Medical Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/9/2011
Publication Date: 11/8/2011
Citation: Palmer, G.H., Brown, W.C., Noh, S.M., Brayton, K.A. 2011. Genome-wide screening and identification of antigens for rickettsial vaccine development. FEMS Immunology and Medical Microbiology. 64:115-119.

Interpretive Summary: A. marginale, the causative agent of anaplasmosis, is the most prevalent tick-borne bacterial pathogen of cattle worldwide. Once exposed to the pathogen during tick feeding, infected animals become anemic, lose weight, and have decreased milk production. In some cases, infection is fatal. The currently available tools to control anaplasmosis rely on antibiotic therapy of clinically affected animals and control of ticks, both of which can prove difficult under range conditions. Thus, the goal of our work is to develop a vaccine to prevent anaplasmosis. Through genome sequencing and bio-informatic analysis, all possible vaccine candidates were identified. The next challenge is to link this microbial proteome to the protective immune response of the bovine host in order to identify those bacterial proteins that will induce protection after vaccination. Three independent screens are described in this paper. When considered together, these screens have narrowed the vaccine candidates to three surface proteins.

Technical Abstract: The capacity to identify immunogens for vaccine development by genome-wide screening has been markedly enhanced by the availability of complete microbial genome sequences coupled to rapid proteomic and bioinformatic analysis. Critical to this genome-wide screening is in vivo testing in the context of a natural host-pathogen relationship, one that includes genetic diversity in the host as well as among pathogen strains. We aggregate the results of three independent genome-wide screens using in vivo immunization and protection against Anaplasma marginale as a model for discovery of vaccine antigens for rickettsial pathogens. In silico analysis identified 62 outer membrane proteins (Omp) from the 949 predicted proteins in the A. marginale genome. These 62 Omps were reduced to 10 vaccine candidates by two-independent genome-wide screens using IgG2 from vaccinates protected from challenge following vaccination with whole outer membranes (screen 1) or bacterial surface complexes (screen 2). Omps with broadly conserved epitopes were identified by immunization with a live heterologous vaccine, A. marginale ss. centrale (screen 3), reducing the candidates to three. The genome-wide screens identified Omps that have orthologues broadly conserved among rickettsial pathogens and highlighted the importance of identifying antigens with immunologically sub-dominant proteins. The results support the use of genome-wide screening based on natural host-pathogen animal models, an approach available to a broader set of rickettsial and bacterial pathogens.