Protein- and DNA-based anthrax toxin vaccines confer protection in guinea pigs against inhalational challenge withBacillus cereusG9241

Abstract

In the past decade, several Bacillus cereus strains have been isolated from otherwise healthy individuals who succumbed to bacterial pneumonia presenting symptoms resembling inhalational anthrax. One strain was indistinguishable from B. cereus G9241, previously cultured from an individual who survived a similar pneumonia-like illness and which was shown to possess a complete set of plasmid-borne anthrax toxin-encoding homologs. The finding that B. cereus G9241 pathogenesis in mice is dependent on pagA1-derived protective antigen (PA) synthesis suggests that an anthrax toxin-based vaccine may be effective against this toxin-encoding B. cereus strain. Dunkin Hartley guinea pigs were immunized with protein- and DNA-based anthrax toxin-based vaccines, immune responses were evaluated and survival rates were calculated after lethal aerosol exposure with B. cereus G9241 spores. Each vaccine induced seroconversion with the protein immunization regimen eliciting significantly higher serum levels of antigen-specific antibodies at the prechallenge time-point compared with the DNA-protein prime-boost immunization schedule. Complete protection against lethal challenge was observed in all groups with a detectable prechallenge serum titer of toxin neutralizing antibodies. For the first time, we demonstrated that the efficacy of fully defined anthrax toxin-based vaccines was protective against lethal B. cereus G9241 aerosol challenge in the guinea pig animal model.

You Can’t B. cereus – A Review of Bacillus cereus Strains That Cause Anthrax-Like Disease

“…Fortunately, as the mechanism of pathogenicity is the same through production of tripartite anthrax toxin, it is highly likely that current anthrax vaccines will provide effective immunity against the atypical B. cereus and Bcbva strains (Oh et al, 2013;Palmer et al, 2014;Brézillon et al, 2015). The bacteria are also susceptible to frontline antibiotics, though administration of secondary β-lactamase antibiotics (such as penicillin) may have reduced efficacy due to inherent resistance in many B. cereus strains (Table 4; Klee et al, 2006).…”

“…As the toxins expressed by atypical B. anthracis and Bcbva strains are homologous to those produced by B. anthracis, it is hypothesized that these currently licensed vaccines will provide adequate protection against anthrax-like disease caused by B. cereus. Studies in C57BL/6 mice and Dunkin Hartley guinea pigs confirmed that vaccination with PA is sufficient to provide protective, though not sterilizing, immunity against B. cereus G9241 (Oh et al, 2013;Palmer et al, 2014). Furthermore, a formaldehyde-inactivated spore and PA preparation generated immunity to Bcbva strains in outbred mice (Brézillon et al, 2015).…”

Antibody response to HER2 extracellular domain and subdomains in mouse following DNA immunization

“…DNA prime-protein boost immunization is an attractive strategy in development of a potent vaccination method by eliciting a more robust immune response to different pathogens including virus, bacteria, and parasites [38][39][40][41]. In cancer setting, this strategy could be potentially applicable in induction of protective immune response to poor immunogenic tumor antigens.…”