Protective Immune Response against Bacillus anthracis Induced by Intranasal Introduction of a Recombinant Adenovirus Expressing the Protective Antigen Fused to the Fc-fragment of IgG2a

abStract Anthrax is a particularly dangerous infectious disease that affects humans and livestock. It is char-acterized by intoxication, serosanguineous skin lesions, development of lymph nodes and internal organs, and may manifest itsself in either a cutaneous or septic form. The pathogenic agent is Bacillus anthracis, a gram-positive, endospore-forming, rod-shaped aerobic bacterium. Efficacious vaccines that can rapidly induce a long-term immune response are required to prevent anthrax infection in humans. In this study, we designed three recombinant human adenovirus serotype-5-based vectors containing various modifications of the fourth domain of the B. anthracis protective antigen (PA). Three PA modifications were constructed: a secretable form (Ad-sPA), a non-secretable form (Ad-cPA), and a form with the protective antigen fused to the Fc fragment of immunoglobulin G2a (Ad-PA-Fc). All these forms exhibited protective properties against Bacillus anthracis. The highest level of protection was induced by the Ad-PA-Fc recombinant adenovirus. Our findings indicate that the introduction of the Fc antibody fragment into the protective antigen significantly improves the protective properties of the Ad-PA-Fc adenovirus against B. anthracis.KeyWordS Bacillus anthracis, immunization, protective antigen, recombinant adenovirus.abbreViationS Аd – adenovirus; PFU – plaque-forming unit; PA – protective antigen; Fc – Fc-fragment of IgG2a; IFA – incomplete Freund’s adjuvant; PBS – phosphate-buffered saline.introductionBacillus anthracis is a gram-positive, endospore-form-ing, rod-shaped aerobic bacterium that causes a dan-gerous infectious disease that affects susceptible ani-mals and humans. Human anthrax cases are reported every year in many countries. Anthrax spores penetrate the body and are absorbed by macrophages, which, in turn, migrate to the local lymph nodes [1]. Inside the macrophages, the spores evolve into a vegetative form, which causes progression of the generalized infection. Due to the B. anthracis pathogenicity, anthrax often becomes an acute, highly lethal disease, unless preven-tive and curative interventions are undertaken on time [2–5].even today, the problem of anthrax prevention re-mains important, because of the yearly sporadic dis-ease outbreaks with lethal outcomes in humans [6, 7]. In russia, a vaccine containing the acapsular strain StI-1 is used for anthrax prevention. However, the live spore vaccine StI-1 has a number of disadvantages, includ-ing the need for annual re-vaccinations, reactogenic-ity, and absence of a strong immunity against certain field isolates circulating in russia [8–12]. the chemi-cal vaccine used in the uSA is not an ideal option, as it requires six-dose vaccination series over 18 months to develop a strong immunity, which causes allergiza-tion of the re-vaccinated organism. taking this factor into account, the issue of further exploring g anthrax