Selection and evaluation of the immunogenicity of protective antigen mutants as anthrax vaccine candidates

Vaccine
Ming YanJulia Y Wang

Abstract

Protective antigen (PA) is a central component of anthrax toxin and a major antigen in anthrax vaccines. However, the use of native PA as a vaccine is not optimal. If administered to people who have been freshly exposed to anthrax, PA may actually aid in anthrax toxin formation and thus may pose a serious safety concern for postexposure vaccination applications. A non-functional PA mutant may be a much safer alternative. To identify an improved anthrax vaccine antigen, we examined four non-functional mutants of PA, each being impaired in a critical step of the cellular intoxication pathway of PA. These mutants were Rec(-) (unable to bind PA-receptors), SSSR (resistant to activation by furin), Oligo(-) (unable to form oligomers), and DNI (Dominant Negative Inhibitory, unable to form endosomal transmembrane pores). When tested in mice and after three doses of immunization, all four mutants were highly potent in eliciting PA-specific, toxin-neutralizing antibodies, with immunogenicity increasing in the order of PA<Rec(-)<SSSR<Oligo(-)<DNI. While the differences between Rec(-) or SSSR and PA were small and not statistically significant, DNI and Oligo(-) were significantly more immunogenic than wild-type PA. One year after immunizat...Continue Reading

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Citations

Aug 18, 2010·Antimicrobial Agents and Chemotherapy·Gaobing WuZiduo Liu
Nov 5, 2008·Expert Review of Vaccines·Alicia Demirjian, Ofer Levy
Sep 5, 2008·Expert Review of Vaccines·Angela M Bodles-Brakhop, Ruxandra Draghia-Akli
Oct 20, 2009·Vaccine·Arthur M Friedlander, Stephen F Little
Sep 5, 2009·Molecular Aspects of Medicine·Robert J CybulskiAlison D O'Brien
Jul 22, 2015·Annual Review of Microbiology·Mahtab MoayeriShihui Liu
Jan 5, 2011·Immunological Reviews·Theodor ChitlaruAvigdor Shafferman
Jul 2, 2016·Scientific Reports·Xudong LiangShulin Dong
Jan 28, 2010·Journal of Medicinal Chemistry·Dimitrios G Bouzianas

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