LIVE ANTIVARIOLIC VACCINES
https://doi.org/10.21055/0370-1069-2017-2-72-77
Abstract
Smallpox eradication due to global vaccination is still one of the paramount triumphs of medical science. Given the termination of the subsequent immunization, nowadays humanity virtually possesses no antivariolic immunity and is unprotected against the pathogenic for humans orthopoxviruses. Utilization of the first-generation traditional live vaccines, obtained with the help of the virus replication on calf skin, or the second-generation preparation, produced in mammalian cell cultures or grown on bird embryos, for mass vaccination is currently unacceptable in view of considerable increase in immune deficiency states among the human population within the recent decades. Attenuated non-replicating antivariolic vaccines of the third generation, obtained in the process of multiple vaccinia virus (VV) passage on cell cultures of heterologous host, induce weaker antivariolic response as compared to traditional vaccine. The most prospective approach is to produce the vaccines of the fourth generation, applying targeted VV genes’ mutation, which control protective reactions of an organism against viral infection, as well as host range genes and the genes involved in nucleic acid metabolism, while skipping the genes responsible for virus replication. Novel attenuated and highly immunogenic strain, VV LIVPΔ6, having mutations in 6 virulence genes, is presently in the phase of pre-clinical trial and later on it may turn an effective and safe vaccine of the fourth generation against smallpox and other orthopoxvirus infections in humans.
About the Author
R. A. Maksyutov
State Scientific Centre of Virology and Biotechnology “Vector”
Russian Federation
Kol’tsovo, Novosibirsk Region, 630559
Russian Federation
Kol’tsovo, Novosibirsk Region, 630559
References
1. Marennikova S.S., Shchelkunov S.N. [Pathogenic for Humans Orthopoxviruses]. M.: KMK Scientific Press Ltd.; 1998. 386 p.
2. Yakubitsky S.N., Kolosova I.V., Maksyutov R.A., Shchelkunov S.N. [Highly immunogenic variant of attenuated vaccinia virus]. Biokhim., Biofiz., Mol. Biol. 2016; 466:241–4.
3. Bell E., Shamim M., Whitbeck J.C., Sfyroera G., Lambris J.D., Isaacs S.N. Antibodies against the extracellular enveloped virus B5R protein are mainly responsible for the EEV neutralizing capacity of vaccinia immune globulin. Virology. 2004; 325:425–31. DOI: 10.1016/j.virol.2004.05.004.
4. Bhanuprakash V., Venkatesan G., Balamurugan V., Hosamani M., Yogisharadhya R., Gandhale P., Reddy K.V., Damle A.S., Kher H.N., Chandel B.S., Chauhan H.C., Singh R.K. Zoonotic infections of buffalopox in India. Zoonoses Public Health. 2010; 57:e149–55. DOI: 10.1111/j.1863-2378.2009.01314.x.
5. Blanchard T.J., Alcami A., Andrea P., Smith G.L. Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine. J. Gen. Virol. 1998; 79:1159–67. DOI: 10.1099/0022-1317-79-5-1159.
6. Campe H., Zimmermann P., Glos K., Bayer M., Bergemann H., Dreweck C., Graf P., Weber B.K., Meyer H., Büttner M., Busch U., Sing A. Cowpox virus transmission from pet rats to humans, Germany. Emerg. Infect. Dis. 2009; 15(5):777–80. DOI: 10.3201/eid1505.090159.
7. Carletti F., Bordi L., Castilletti C., Di Caro A., Falasca L., Gioia C., Ippolito G., Zaniratti S., Beltrame A., Viale P., Capobianchi M.R. Cat-to-human orthopoxvirus transmission northeastern Italy. Emerg. Infect. Dis. 2009; 15(3):499–500. DOI: 10.3201/eid1503.080813.
8. Denes B., Gridley D.S., Fodor N., Takatsy Z., Timiryasova T.M., Fodor I. Attenuation of a vaccine strain of vaccinia virus via inactivation of interferon viroceptor. J. Gene Med. 2006; 8(7):814–23. DOI: 10.1002/jgm.907.
9. Drexler I., Heller K., Wahren B., Erfle V., Sutter G. Highly attenuated modified vaccinia virus Ankara replicates in baby hamster kidney cells, a potential host for virus propagation, but not in various human transformed and primary cells. J. Gen. Virol. 1998; 79:347–52. DOI: 10.1099/0022-1317- 79-2-347.
10. Ducournau C., Ferrier-Rembert A., Ferraris O., Joffre A., Favier A.L., Flusin O., Van Cauteren D., Kecir K., Auburtin B., Védy S., Bessaud M., Peyrefitte C.N. Concomitant human infections with 2 cowpox virus strains in related cases, France, 2011. Emerg. Infect. Dis. 2013; 19(12):1996–9. DOI: 10.3201/eid1912.130256.
11. Earl P.L., Americo J.L., Wyatt L.S., Eller L.A., Whitbeck J.C., Cohen G.H., Eisenberg R.J., Hartmann C.J., Jackson D.L., Kulesh D.A., Martinez M.J., Miller D.M., Mucker E.M., Shamblin J.D., Zwiers S.H., Huggins J.W., Jahrling P.B., Moss B. Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox. Nature. 2004; 428(6979):182–5. DOI: 10.1038/nature02331.
12. Fenner F. Risks and benefits of vaccinia vaccine use in the worldwide smallpox eradication campaign. Res. Virol. 1989; 140(5):465–6.
13. Fenner F., Henderson D.A., Arita I., Jezek Z., Ladnyi I.D. Smallpox and its eradication. World Health Organization: Geneva; 1988. 1460 p.
14. Ferrier-Rembert A., Drillien R., Meignier B., Garin D., Crance J.M. Safety, immunogenicity and protective efficacy in mice of a new cell-cultured Lister smallpox vaccine candidate. Vaccine. 2007; 25(49):8290–7. DOI: 10.1016/j.vaccine.2007.09.050.
15. Frey S.E., Newman F.K., Kennedy J.S., Ennis F., Abate G., Hoft D.F., Monath T.P. Comparison of the safety and immunogenicity of ACAM1000, ACAM2000 and Dryvax® in healthy vaccinia-naive adults. Vaccine. 2009; 27(10):1637–44. DOI: 10.1016/j.vaccine.2008.11.079.
16. Hekker A.C., Bos J.M., Rai N.K., Keja J., Cuboni G., Emmet B., Djalins J. Large-scale use of freeze-dried smallpox vaccine prepared in primary ultures of rabbit kidney cells. Bull. World Health Organ. 1976; 54(3):279–84.
17. Hirayama M. Smallpox vaccination in Japan. In: Fukumi H., editor. The vaccination theory and practice. Tokyo: International Medical Foundation of Japan; 1975.
18. Hobi S., Mueller R.S., Hill M., Nitsche A., Löscher T., Guggemos W., Ständer S., Rjosk-Dendorfer D., Wollenberg A. Neurogenic inflammation and colliquative lymphadenitis with persistent orthopox virus DNA detection in a human case of cowpox virus infection transmitted by a domestic cat. Br. J. Dermatol. 2015; 173(2):535–9. DOI: 10.1111/bjd.13700.
19. Isaacs S.N., Kotwal G.J., Moss B. Vaccinia virus complement-control protein prevents antibody-dependent complement-enhanced neutralization of infectivity and contributes to virulence. Proc. Natl. Acad. Sci. USA. 1992; 89(2):628–32.
20. Jacobs B.L., Langland J.O., Kibler K.V., Denzler K.L., White S.D., Holechek S.A., Wong S., Huynh T., Baskin C.R. Vaccinia virus vaccines: past, present and future. Antiviral Res. 2009; 84(1):1–13. DOI: 10.1016/j.antiviral.2009.06.006.
21. Johnson B.F., Kanatani Y., Fujii T., Saito T., Yokote H., Smith G.L. Serological responses in humans to the smallpox vaccine LC16m8. J. Gen. Virol. 2011; 92:2405–10. DOI: 10.1099/vir.0.034207-0.
22. Kinnunen P.M., Holopainen J.M., Hemmilä H., Piiparinen H., Sironen T., Kivelä T., Virtanen J., Niemimaa J., Nikkari S., Järvinen A., Vapalahti O. Severe Ocular Cowpox in a Human, Finland. Emerg. Infect. Dis. 2015; 21(12):2261–3. DOI: 10.3201/eid2112.150621.
23. Lane J.M., Ruben F.L., Neff J.M., Millar J.D. Complications of smallpox vaccination, 1968: results of ten statewide surveys. J. Infect. Dis. 1970; 122(4):303–9.
24. Levine R.S., Peterson A.T., Yorita K.L., Carroll D., Damon I.K., Reynolds M.G. Ecological niche and geographic distribution of human monkeypox in Africa. PLoS One. 2007; 2(1):е176. DOI: 10.1371/journal.pone.0000176.
25. Maluquer de Motes C., Cooray S., Ren H., Almeida G.M., McGourty K., Bahar M.W., Stuart D.I., Grimes J.M., Graham S.C., Smith G.L. Inhibition of apoptosis and NF-κB activation by vaccinia protein N1 occur via distinct binding surfaces and make different contributions to virulence. PLoS Pathog. 2011; 7(12):e1002430. DOI: 10.1371/journal.ppat.1002430.
26. McCurdy L.H., Larkin B.D., Martin J.E., Graham B.S. Modified vaccinia Ankara: potential as an alternative smallpox vaccine. Clin. Infect. Dis. 2004; 38(12):1749–53. DOI: 10.1086/421266.
27. Meyer H., Sutter G., Mayr A. Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence. J. Gen. Virol. 1991; 72:1031–8. DOI: 10.1099/0022-1317-72-5-1031.
28. Midgley C.M., Putz M.M., Weber J.N., Smith G.L. Vaccinia virus strain NYVAC induces substantially lower and qualitatively different human antibody responses compared with strains Lister and Dryvax. J. Gen. Virol. 2008; 89:2992–7. DOI: 10.1099/vir.0.2008/004440-0.
29. Monath T.P., Caldwell J.R., Mundt W., Fusco J., Johnson C.S., Buller M., Liu J., Gardner B., Downing G., Blum P.S., Kemp T., Nichols R., Weltzin R. ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health strain) – a second-generation smallpox vaccine for biological defense. Int. J. Infect. Dis. 2004; 8:S31–44. DOI: 10.1016/j.ijid.2004.09.002.
30. Morikawa S., Sakiyama T., Hasegawa H., Saijo M., Maeda A., Kurane I., Maeno G., Kimura J., Hirama C., Yoshida T., Asahi-Ozaki Y., Sata T., Kurata T., Kojima A. An attenuated LC16m8 smallpox vaccine: analysis of full-genome sequence and induction of immune protection. J. Virol. 2005; 79(18):11873–91. DOI: 10.1128/JVI.79.18.11873-11891.2005.
31. Murphy F.A., Osburn B.I. Adventitious agents and smallpox vaccine in strategic national stockpile. Emerg. Infect. Dis. 2005; 11(7):1086–9. DOI: 10.3201/eid1107.050277.
32. Ninove L., Domart Y., Vervel C., Voinot C., Salez N., Raoult D., Meyer H., Capek I., Zandotti C., Charrel R.N. Cowpox virus transmission from pet rats to humans, France. Emerg. Infect. Dis. 2009; 15(5):781–4. DOI: 10.3201/eid1505.090235.
33. Parker S., Nuara A., Buller R.M., Schultz D.A. Human monkeypox: an emerging zoonotic disease. Future Microbiol. 2007; 2(1):17–34. DOI: 10.2217/17460913.2.1.17.
34. Poland G.A., Grabenstein J.D., Neff J.M. The US smallpox vaccination program: a review of a large modern era smallpox vaccination implementation program. Vaccine. 2005; 23(17–18):2078–81. DOI: 10.1016/j.vaccine.2005.01.012.
35. Rehm K.E., Connor R.F., Jones G.J., Yimbu K., Roper R.L. Vaccinia virus A35R inhibits MHC class II antigen presentation. Virology. 2010; 397(1):176–86. DOI: 10.1016/j.virol.2009.11.008.
36. Riedel S. Edward Jenner and the history of smallpox and vaccination. Proc. (Bayl. Univ. Med. Cent.). 2005; 18(1):21–5.
37. Rimoin A.W., Kisalu N., Kebela-Ilunga B., Mukaba T., Wright L.L., Formenty P., Wolfe N.D., Shongo R.L., Tshioko F., Okitolonda E., Muyembe J.J., Ryder R.W., Meyer H. Endemic human monkeypox, Democratic Republic of Congo, 2001–2004. Emerg. Infect. Dis. 2007; 13(6): 934–7. DOI: 10.3201/eid1306.061540.
38. Rimoin A.W., Mulembakani P.M., Johnston S.C., Lloyd Smith J.O., Kisalu N.K., Kinkela T.L., Blumberg S., Thomassen H.A., Pike B.L., Fair J.N., Wolfe N.D., Shongo R.L., Graham B.S., Formenty P., Okitolonda E., Hensley L.E., Meyer H., Wright L.L., Muyembe J.J. Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo. Proc. Natl. Acad. Sci. USA. 2010; 107(37):16262–7. DOI: 10.1073/pnas.1005769107.
39. Shchelkunov S.N. Emergence and reemergence of smallpox: the need in development of a new generation smallpox vaccine. Vaccine. 2011; 29:D49–53. DOI: 10.1016/j.vaccine.2011.05.037.
40. Shchelkunov S.N. An increasing danger of zoonotic orthopoxvirus infections. PLoS Pathog. 2013; 9(12):e1003756. DOI: 10.1371/journal.ppat.1003756.
41. Shida H., Hinuma Y., Hatanaka M., Morita M., Kidokoro M., Suzuki K., Maruyama T., Takahashi-Nishimaki F., Sugimoto M., Kitamura R. Effects and virulences of recombinant vaccinia viruses derived from attenuated strains that express the human T-cell leukemia virus type I envelope gene. J. Virol. 1988; 62(12):4474–80.
42. Silva-Fernandes A.T., Travassos C.E., Ferreira J.M., Abrahão J.S., Rocha E.S., Viana-Ferreira F., dos Santos J.R., Bonjardim C.A., Ferreira P.C., Kroon E.G. Natural human infections with Vaccinia virus during bovine vaccinia outbreaks. J. Clin. Virol. 2009; 44(4):308–13. DOI: 10.1016/j.jcv.2009.01.007.
43. Smith G.L., Benfield C.T., Maluquer de Motes C., Mazzon M., Ember S.W., Ferguson B.J., Sumner R.P. Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity. J. Gen. Virol. 2013; 94:2367–92. DOI: 10.1099/vir.0.055921-0.
44. Tartaglia J., Cox W.I., Pincus S., Paoletti E. Safety and immunogenicity of recombinants based on the genetically-engineered vaccinia strain, NYVAC. Dev. Biol. Stand. 1994; 82:125–9.
45. Taylor G., Stott E.J., Wertz G., Ball A. Comparison of the virulence of wild-type thymidine kinase (tk)-deficient and tk+ phenotypes of vaccinia virus recombinants after intranasal inoculation of mice. J. Gen. Virol. 1991; 72:125–30. DOI: 10.1099/0022-1317-72-1-125.
46. The global eradication of smallpox, final report of the global commission for the certification of smallpox eradication, Geneva, December 1979. World Health Organization: Geneva; 1980.
47. Trindade G.S., Guedes M.I., Drumond B.P., Mota B.E., Abrahao J.S., Lobato Z.I., Gomes J.A., Corrêa-Oliveira R., Nogueira M.L., Kroon E.G., da Fonseca F.G. Zoonotic vaccinia virus: clinical and immunological characteristics in a naturally infected patient. Clin. Infect. Diseases. 2009; 48(3):е37–40. DOI: 10.1086/595856.
48. Wiser I., Balicer R.D., Cohen D. An update on smallpox vaccine candidates and their role in bioterrorism related vaccination strategies. Vaccine. 2007; 25(3):976–84. DOI: 10.1016/j.vaccine.2006.09.046.
49. Yakubitsky S.N., Kolosova I.V., Maksyutov R.A., Shchelkunov S.N. Attenuation of Vaccinia Virus. Acta Naturae. 2015; 7(4):113–21.
50. Zafar A., Swanepoel R., Hewson R., Nizam M., Ahmed A., Husain A., Grobbelaar A., Bewley K., Mioulet V., Dowsett B., Easterbrook L., Hasan R. Nosocomial buffalopoxvirus infection, Karachi, Pakistan. Emerg. Infect. Dis. 2007; 13(6):902–4. DOI: 10.3201/eid1306.061068.
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For citations:
Maksyutov R.A. LIVE ANTIVARIOLIC VACCINES. Problems of Particularly Dangerous Infections. 2017;(2):72-77. (In Russ.) https://doi.org/10.21055/0370-1069-2017-2-72-77
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