Abstract
A commercial Bacillus anthracis (Anthrax) whole genome protein microarray has been used to identify immunogenic Anthrax proteins (IAP) using sera from groups of donors with (a) confirmed B. anthracis naturally acquired cutaneous infection, (b) confirmed B. anthracis intravenous drug use-acquired infection, (c) occupational exposure in a wool-sorters factory, (d) humans and rabbits vaccinated with the UK Anthrax protein vaccine and compared to naïve unexposed controls. Anti-IAP responses were observed for both IgG and IgA in the challenged groups; however the anti-IAP IgG response was more evident in the vaccinated group and the anti-IAP IgA response more evident in the B. anthracis-infected groups. Infected individuals appeared somewhat suppressed for their general IgG response, compared with other challenged groups. Immunogenic protein antigens were identified in all groups, some of which were shared between groups whilst others were specific for individual groups. The toxin proteins were immunodominant in all vaccinated, infected or other challenged groups. However, a number of other chromosomally-located and plasmid encoded open reading frame proteins were also recognized by infected or exposed groups in comparison to controls. Some of these antigens e.g., BA4182 are not recognized by vaccinated individuals, suggesting that there are proteins more specifically expressed by live Anthrax spores in vivo that are not currently found in the UK licensed Anthrax Vaccine (AVP). These may perhaps be preferentially expressed during infection and represent expression of alternative pathways in the B. anthracis “infectome.” These may make highly attractive candidates for diagnostic and vaccine biomarker development as they may be more specifically associated with the infectious phase of the pathogen. A number of B. anthracis small hypothetical protein targets have been synthesized, tested in mouse immunogenicity studies and validated in parallel using human sera from the same study.
Highlights
Bacillus anthracis is a large Gram-positive spore-forming, rodshaped bacterium that is the etiological agent of the zoonotic disease Anthrax
Anthrax positive intravenous drug users (IVDU) (AP IVDU) and Anthrax negative IVDU (AN IVDU) sera were not retested due to insufficient sera remaining from routine clinical testing
All human control sera were assigned to their respective test groups according to geographical recruitment/vaccination or exposure history and positive anti-toxin titers for the AVP vaccines (AVPV), Turkish cutaneous Anthrax patient (TCA) and Belgian wool-sorters (BWS) group
Summary
Bacillus anthracis is a large Gram-positive spore-forming, rodshaped bacterium that is the etiological agent of the zoonotic disease Anthrax. Disease may be contracted through either direct contact with infected animals, or within industrialized countries, through contact with animal by-products such as wool, skins, (Wattiau et al, 2009) or bone meal, where spores can survive in the environment for decades (Jernigan et al, 2001; Olano and Walker, 2011) This occurs when spores enter the body through breaks in the skin, via ingestion or by inhalation (Little and Ivins, 1999). After a critical turning point, these forms of the disease no longer respond to treatment and the patient succumbs to overwhelming septicaemia and toxic shock (Baillie and Read, 2001) This is due to release of various toxins by the Anthrax bacillus formed of edema factor (EF) or lethal factor (LF) and protective antigen (PA) (Liu et al, 2014), the genes for which are carried on a plasmid pXO1. The toxin proteins have as a consequence been under development by a number of commercial groups as sub-unit vaccine candidates for Anthrax infection (Brey, 2005; Splino et al, 2005; Comer and Peterson, 2009; Friedlander and Little, 2009; Altmann, 2015)
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