Humoral immunity, vaccination period and demographic characteristics of first immunized smallpox vaccine recipients

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General vaccination of population with vaccinia virus leaded to the eradication of smallpox, then it was finished because of the danger of adverse events. The recurrence of research interest in smallpox vaccine is due to the research of using the virus as a weapon of bioterrorism and the increased frequency of orthopoxvirus infections whereas the population immunity decline. The vaccinia virus is also used as a vector for creating recombinant vaccines. Understanding the pathway and predicting the immune response it will be able to avoid possible adverse events and excessive immunization. The aim of the study was to assess the correlations between humoral immunity, clinical signs during a vaccination period, sex and age characteristics of adults who had received several doses of vaccinia virus. We studied a vaccination clinical data of 135 subjects revaccinated with a smallpox vaccine from twice to 10 times. A total of 95% and 5% vaccine recipients experienced mild or moderate vaccination period, respectively. Inoculation skin lesions was noted at 127 subjects (94.1%). Among them more than 22% vaccine recipients experienced local or systemic adverse events. Compared to mild group moderate group had larger hyperemia (p = 0.04), scab (p = 0.01), healing time (p = 0.001). The age subjects with a moderate vaccination period is less than mild (p = 0.03), the chance of lymphadenopathy development is higher within moderate vaccination period (p < 0.001). Vaccinia neutralizing antibody titers were determined for 54 subjects using plaque reduction neutralization tests. There was a noted tendency of higher protective antibody values at women compared with men. Negative correlation between the antibody titers and the hyperemia size was revealed. Frequently axillary adenopathy is assotiated with higher protective antibody values. Vaccinia neutralizing antibody titers value are not associated with the presence and size of the lesion, the scab falling time, age and the number of previous vaccinations. The clinical variability and the immune response using the same vaccine and the same pattern vaccination would be explained by individual genetic differences that should be further explored.

About the authors

O. S. Ermilova

State Scientific Centre of Virology and Biotechnology Vector of Rospotrebnadzor


Junior Researcher.


Russian Federation

Z. I. Gin’ko

Medical and Sanitary Part No.163 of the Federal Medical and Biological Agency


Infectious Disease Physician, Medical Sanitary Station No. 163.


Russian Federation

V. A. Belyavskaya

State Scientific Centre of Virology and Biotechnology Vector of Rospotrebnadzor

Author for correspondence.

Valentina A. Belyavskaya - PhD, MD (Biology), Professor, Leading Researcher.

630559, Novosibirsk Region, Koltsovo, Phone: +7 (383) 336-47-00

Russian Federation


  1. Ермилова О.С., Гинько З.И., Белявская В.А., Кузубов В.И., Сергеев Ар.А., Горбатовская Д.О., Азаев М.Ш., Агафонов А.П., Воевода М.И., Сергеев А.Н. Анализ особенностей течения вакцинального процесса у лиц, привитых оспенной живой вакциной, при первичной и повторных вакцинациях // Проблемы особо опасных инфекций. 2015. № 1. С. 75—78. doi: 10.21055/0370-1069-2015-1-75-78
  2. Зверев В.В., Бойченко М.Н. Медицинская микробиология, вирусология и иммунология. М.: ГЭОТАР-Медиа, 2010. 448 с.
  3. Закс Л. Статистическое оценивание. М.: Статистика, 1976. 598 с.
  4. Bossi P., Gay F., Fouzai I., Combadiere B., Brousse G., Lebrun-Vignes B., Crance J.M., Autran B., Garin D. Demographic and clinical factors associated with response to smallpox vaccine in preimmunized volunteers. PLoS One, 2008, vol. 3, no. 12: e4087. doi: 10.1371/journal.pone.0004087
  5. Bhatia A., Sekhon H.K., Kaur G. Sex hormones and immune dimorphism. The Scientific World Journal, 2014, vol. 2014, 8 p. doi: 10.1155/2014/159150
  6. Cook I.F. Sexual dimorphism of humoral immunity with human vaccines. Vaccine, 2008, vol. 26, no. 29-30, pp. 3551-3555. doi: 10.1016/j.vaccine.2008.04.054
  7. Crotty S., Felgner P., Davies H., Glidewell J., Villarreal L., Ahmed R. Cutting edge: long-term B cell memory in humans after smallpox vaccination. J. Immunol., 2003, vol. 171, no. 10, pp. 4969-4973. doi: 10.4049/jimmunol.171.10.4969
  8. Dommguez A., Plans P., Costa J., Torner N., Cardenosa N., Batalla J., Plasencia A., Salleras L. Seroprevalence of measles, rubella, and mumps antibodies in Catalonia Spain: results of a cross-sectional study. Eur. J. Clin. Microbiol. Infect. Dis., 2006, vol. 25, no. 5, pp. 310-317. doi: 10.1007/s10096-006-0133-z
  9. Grondahl-Yli-Hannuksela K., Vahlberg T., Ilonen J., Mertsola J., He Q. Polymorphism of IL-10 gene promoter region: association with T cell proliferative responses after acellular pertussis vaccination in adults. Immunogenetics, 2016, vol. 68, no. 9, pp. 733-741. doi: 10.1007/s00251-016-0923-0
  10. 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, vol. 92, no. 10, pp. 2405-2410. doi: 10.1099/vir.0.034207-0
  11. Hammarlund E., Lewis M.W., Hansen S.G., Strelow L.I., Nelson J.A., Sexton G.J., Hanifin J.M., Slifka M.K. Duration of antiviral immunity after smallpox vaccination. Nat. Med., 2003, vol. 9, no. 19, pp. 1131-1137. doi: 10.1038/nm917
  12. Kennedy R.B., Ovsyannikova I.G., Pankratz V.S., Vierkant R.A., Jacobson R.M., Ryan MA, Poland G.A. Gender effects on humoral immune responses to smallpox vaccine. Vaccine, 2009, vol. 27, no. 25-26, pp. 3319-3323. doi: 10.1016/j.vaccine.2009.01.086
  13. Kim N.H., Kang Y.M., Kim G., Choe P.G., Song J.S., Lee K.H., Seong B.L., Park W.B., Kim N.J., Oh M.D. An open-label, single arm, phase III clinical study to evaluate the efficacy and safety of CJ smallpox vaccine in previously vaccinated healthy adults. Vaccine, 2013, vol. 31, no. 45, pp. 5239- 5242. doi: 10.1016/j.vaccine.2013.08.071
  14. Klein N.P., Holmes T.H., Sharp M.A., Heineman T.C., Schleiss M.R., Bernstein D.I., Kemble G., Arvin A.M., Dekker C.L. Variability and gender differences in memory T cell immunity to varicellazoster virus in healthy adults. Vaccine, 2006, vol. 24, no. 33-34, pp. 5913-5918. doi: 10.1016/j.vaccine.2006.04.060
  15. Kwanchum K., Ampol S., Thongput A., Horthongkham N., Udomphunthurak S., Siritantikorn S., Kantakamalakul W. Duration of neutralizing antibody persisting in Thai individuals after childhood vaccination against smallpox. Asian Pac. J. Allergy Immunol., 2017, vol. 35, no. 4, pp. 239-243. doi: 10.12932/AP0857
  16. Liu Q., Huang W., Nie J., Zhu R., Gao D., Song A., Meng S., Xu X., Wang Y. A novel high-throughput vaccinia virus neutralization assay and preexisting immunity in populations from different geographic regions in China. PLoS One, 2012, vol. 7, no. 3. doi: 10.1371/journal.pone.0033392
  17. Orr N., Forman M., Marcus H., Lustig S., Paran N., Grotto I., Klement E., Yehezkelli Y., Robin G., Reuveny S., Shafferman A., Cohen D. Clinical and immune responses after revaccination of israeli adults with the lister strain of vaccinia virus. J. Infect. Dis., 2004, vol. 190, no. 7, pp. 1295-1302. doi: 10.1086/423851
  18. Taub D.D., Ershler W.B., Janowski M., Artz A., Key M.L., McKelvey J., Muller D., Moss B., Ferrucci L., Duffey P.L., Longo D.L. Immunity from smallpox vaccine persists for decades: a longitudinal study. Am. J. Med., 2008, vol. 121, no. 12, pp. 1058—1064. doi: 10.1016/j.amjmed.2008.08.019
  19. Saito T., Fujii T., Kanatani Y., Saijo M., Morikawa S., Yokote H., Takeuchi T., Kuwabara N. Clinical and immunological response to attenuated tissue-cultured smallpox vaccine LC16m8. JAMA, 2009, vol. 103, no. 10, pp. 1025—1033. doi: 10.1001/jama.2009.289
  20. Verardi P.H., Titong A., Hagen C.J. A vaccinia virus renaissance: new vaccine and immunotherapeutic uses after smallpox eradication. Hum. Vaccin. Immunother., 2012, vol. 8, no. 7, pp. 961—970. doi: 10.4161/hv.21080

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Copyright (c) 2021 Ermilova O.S., Gin’ko Z.I., Belyavskaya V.A.

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