Mono- and multipathogen anti-peptide antibodies for passive immunization or treatment of the biothreat agents Bacillus anthracis, Yersinia pestis, and Francisella tularensis

Abstract

As etiological agents of anthrax, plague, and tularemia, which can be used as biological weapons, the United States Centers for Disease Control and Prevention (CDC) has classified Bacillus anthracis, Yersinia pestis, and Francisella tularensis as Category A pathogens. Currently, the response to a bioterrorist attack utilizing these agents would be largely reactive as there are no approved vaccines for general public use. Post-exposure antibiotic treatment is effective if it is administered shortly after exposure to the pathogens and due to their long term treatment schedule, the antibiotics tend to be associated with well-known severe side effects. Antibodies that are highly specific for traditional virulence factors associated with the pathogens represent a beneficial addition to the treatment regimen; however, their effectiveness is limited against genetically modified organisms. The conducted research aims to (1) identify non-traditional, virulence-enhancing factors, (2) select restricted peptide epitopes using bioinformatics tools and chemically synthesize them, (3) generate affinity purified antibodies against the selected peptides, and (4) test the efficacy in animal models of anthrax, plague, and tularemia. Furthermore, this study presents a novel concept of multipathogen antigens that are effective against two or more organisms and can be synthesized by either identifying conserved sequences between pathogens or synthesizing chimeric peptides composed of multiple epitopes. The findings revealed mono- and multipathogen therapeutic antibody candidates against anthrax, plague, and tularemia that provide a significant increase in the survival when compared to the conventional antibiotic, ciprofloxacin. Histopathological observations demonstrated that antibodies significantly reduce organ and tissue damage caused by the infections when compared to ciprofloxacin alone. The identification techniques developed and tested in this study represent a novel approach to creating mono- and multipathogen therapeutic antibodies that may be utilized in treating severe infectious diseases.