ИСТИНА

Anthrax is one of ancient diseases that still occur in the world. It is caused by a gram­positive spore­forming bacterium Bacillus anthracis. Anthrax outcomes are extremely harmful for northern agricultural holdings. Moreover, B. anthracis spores could potentially serve as a biological weapon. Thus, the development of effective anthrax vaccines with a long shelf­life is desirable. Anthrax protective antigen (PA) is a main anthrax toxin component. It is a 83 kDa protein that consists of four domains. PA is a key component of existing and currently being developed anthrax vaccines. The main problem associated with using recombinant PA (rPA) in vaccines is its low stability. rPA instability is mainly due to deamidation of certain asparagines and to presence of furin and chymotrypsin cleavage sites in the amino acid sequence. We designed a recombinant protein rPA1+2 containing PA domains I and II with genetically inactivated furin and chymotripsine cleavage sites (162NSRKKR167 sequence was substituted with 162QSSNKE167 and 313FF314 fragment was deleted) and a recombinant protein rPA3+4 containing PA domains III and IV with the most deamidation­prone Asn713 and Asn719 replaced by Gln. Previously published in: Ryabchevskaya EM et al. (2021) Hum Vaccin Immunother 17(2):560­565. Both rPA3+4 and rPA1+2 were demonstrated to remain stable for at least 19 days at +37°С and for at least 160 days at +25°С. Given the fact that PA’s protectivity is not only attributed to a full­size protein, rPA1+2 and rPA3+4 should be an appropriate basis for a stable modern anthrax vaccine. To support this idea, the vaccine formulation containing tobacco mosaic virus­based spherical particles (SPs), which are innovative platform­adjuvant, was developed. The possibility of simultaneous adsorption of rPA1+2 and rPA3+4 to the SPs surface was proved. We propose SPs­rPA1+2­rPA3+4 compositions as a new generation stable anthrax vaccine candidate. Funding: Russian Science Foundation (Grant 18­14­00044).