Approaches to Reduce Adverse Effect of Vaccinia Virus in Orally Immunized Mice

Objective of the investigation was to model the adverse action of vaccinia virus (VV), caused by oral immunization of mice and to evaluate efficacy of its reduction, using therapeutic and prophylactic drugs. Materials and methods. Virological and immunological research methods were used. Results and conclusions. Reproduced was pathological action of VV in the orally infected mice. The ability to reduce the side effect and protect mice from lethal infection was demonstrated by such preparations as Metisazon, Likopid, and NIOCH-14 orally administered in the investigated schemes. Moreover preliminary single oral immunization with TEOVak smallpox vaccine before oral infection with Neurovaccine-92 strain of VV also lowered pathogenic effect and protected mice against death. All the investigated schemes of drug administration did not affect the immune response if used alongside with TEOVak smallpox vaccine and can be deployed to develop safe schemes of primary oral vaccination against smallpox. In addition, such drugs as Ribomunil, Immudon, Ingavirin can be used as means to enhance the immune response to smallpox vaccines.

ортопоксвирус, вирус вакцины, первичное оспопрививание, вирус натуральной оспы, таблетированная оспенная вакцина, поствакцинальные осложнения, orthopoxvirus, vaccinia virus, primary vaccination, variola virus, oral smallpox vaccine, adverse vaccine reactions

1. Borisevich S.V., Marennikova S.S., Makhlay A.A., Terent’ev A.I., Loginova S.Ya., Perekrest V.V., Krasnyansky V.P., Bondarev V.P. [Monkeypox: peculiarities of dissemination after cancellation of the obligatory smallpox vaccination]. Zh. Mikrobiol. Epidemiol. Immunobiol. 2012; 2:69–73.

2. Vorob’ev A.A., Podkuiko V.N., Maksimov V.A. [Oral vaccine against smallpox (concerning the return of smallpox vaccination)]. RAMS Bulletin. 2003; 1:5–10.

3. Zaks L. [Statistical Evaluation]. M.: “Statistika”; 1976. 598 p.

4. Kabanov A.S., Sergeev Al.A., Shishkina L.N., Bulychev L.E., Skarnovich M.O., Sergeev Ar.A., Bormotov N.I., P’yankov O.V., Serova O.A., Bodnev S.A., Selivanov B.A., Tikhonov A.Ya., Agafonov A.P., Sergeev A.N. [Comparative analysis of anti-viral activity of chemical compositions towards Orthopoxviruses experimentally in vivo]. Vopr. Virusol. 2013; (4):39–43.

5. Loginova S.Ya., Borisevich S.V., Maksimov V.A., Bondarev V.P., Perekrest V.V., Shuster A.M. [Relief of post-vaccinal complications after smallpox immunization with interferon inducers]. Khimioterapiya i Antibiotiki. 2010; 1–2:6–11.

6. Onishchenko G.G., Sandakhchiev L.S., Netesov S.V., Martynyuk R.A. [Bioterrorism: national and global threat]. RAS Bulletin. 2003; 73(3):195–204.

7. Berhanu A., King D.S., Mosier S., Jordan R., Jones K.F., Hruby D.E., Grosenbach D.W. ST-246 inhibits in vivo poxvirus dissemination, virus shedding, and systemic disease manifestation. Antimicrob Agents Chemother. 2009; 53(12):4999–5009. DOI: 10.1128/AAC.00678-09.

8. Elsendoorn A., Agius G., Le Moal G., Aajaji F., Favier A-L., Wierzbicka-Hainault E., Béraud G., Flusin O., Crance J-M., Roblot F. Severe ear chondritis due to cowpox virus transmitted by a pet rat. J. Infecti. 2011; 63(5):391–3. DOI: 10.1016/j.jinf.2011.06.004.

9. Fisher R.W., Reed J.L., Snoy P.J., Mikolajczyk, Bray M., Scott D.E., Kennedy M.C. Postexposure prevention of progressive vaccinia in SCID mice treated with vaccinia immune globulin. Clin. Vaccine Immunol. 2011; 18(1):67–74. DOI: 10.1128/CVI.00280-10.

10. Goulding J., Bouge R., Tahiliani V., Croft M., Salek-Ardakani S. CD8 T cells are essential for recovery from a respiratory vaccinia virus infection. J. Immunol. 2012; 189(5):2432–40. DOI: 10.4049/jimmunol.1200799.

11. Green S., Ennis F.A., Mathew A. Long term recall of memory CD8 T cells in mice to first and third generation smallpox vaccines. Vaccine. 2011; 29(8):1666–76. DOI: 10.1016/j.vaccine.2010.12.036.

12. Reed K.D., Melski J.W., Graham M.B., Regnery R.L., Sotir M.J., Wegner M.V., Kazmierczak J.J., Stratman E.J., Li Y., Fairley J.A., Swain G.R., Olson V.A., Sargent E.K., Kehl S.C., Frace M.A., Kline R., Foldy S.L., Davis J.P., Damon I.K. The detection of monkeypox in humans in the Western Hemisphere. N. Engl. J. Med. 2004; 350(4):342–50. DOI: 10.1056/NEJMoa032299.

13. Vellozzi C., Averhoff F., Lane J.M., Wen X., Moore A.C., Santibanez S., Kroger A., Hasbrouck L.M., Kennedy A., Casey C.G. Superinfection following smallpox vaccination (Vaccinia), United States: surveillance January 2003 through January 2004. Clin. Infect. Dis. 2004; 39(11):1660–6. DOI: 10.1086/425617.