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Immunogenicity and efficacy studies of Endo H in vivo deglycosylated Protective Antigen from Bacillus anthracis as a vaccine candidate against anthrax

Mamedov, T;Gun, N;Gulec, B;Khozeini, H;Ungor, R;Yuksel, D;Arslan, A;Dilik, Z;Deniz, D;Goven, N;Mammadova, G;Hasanova, G;

Protective antigen (PA) of B. anthracis is a key component of the anthrax toxin and have been demonstrated as a main immunogenic in the development of subunit vaccine against anthrax. However, the use of recombinant PA (rPA) as a vaccine candidate has faced challenges due to its inherent chemical instability, associated with the spontaneous deamidation of multiple asparagine (Asn) residues in PA molecule. We hypothesized that Endo H in vivo deglycosylated PA83 (dPA83(E)) may be an ideal candidate for PA83-based vaccine development because this technology could eliminate the deamidation of asparagine residues in the PA83 molecule and allow the production of PA83 protein in a deglycosylated, native-like form. In this study, we conducted immunogenicity and challenge efficacy studies of dPA83(E) antigen. We show that plant-produced dPA83(E) antigen demonstrated superior properties over PNGase F in vivo deglycosylated or glycosylated PA83 counterparts and elicited high toxin neutralizing antibody titers in mice and guinea pigs. Furthermore, a single administration of this vaccine candidate protected guinea pigs 100% from fatal B. anthracis infection. Taken together, our results demonstrate that Endo H in vivo enzymatic deglycosylated PA83 is a promising candidate for the development of cost-effective, safe, stable, and highly immunogenic vaccine against anthrax.