Correlations between Humoral Immunity, Vaccination Period and Demographic Characteristics of First Immunized Smallpox Vaccine Recipients

Relevance. After vaccination against smallpox is completed, more than 50% of the population are not immune to pathogens of the genus Orthopoxvirus, which creates the risk of mass infection if the smallpox virus is used as a biological weapon.

Aim. To assess the correlations between humoral immunity, clinical signs during a vaccination period and, sex and age characteristics of vaccinia virus Practical Aspects of Epidemiology and Vaccine Prevention (VCV) recipients.

Materials and methods. We studied a vaccination clinical data of 82 subjects first vaccinated with a smallpox vaccine. Vaccinia neutralizing antibody titers were determined for 27 subjects using plaque reduction neutralization tests. According to antibody titers they were divided into groups of mild (25%), moderate (50%), and heavy reaction (25%).

Results. A total of 34% and 66% vaccine recipients experienced mild or moderate vaccination period, respectively. Among them 83% vaccine recipients experienced or local and systemic adverse events. Compared to mild group, moderate group had larger scab, hyperemia (p < 0,01) and pustules (p < 0,05). It was a tendency that men had smaller scabs, more rapid scab shedding and less intense hyperemia compared to women. In contrast to low and high neutralizing antibody titers, medium ones were associated with smaller local inflammation (induration zones, hyperemia, pustules).

Conclusion. The same vaccine and vaccination schedule may produce different protective neutralizing antibody levels and different humoral immunity in similar demographic groups. The underlying reasons need further research.

1. WHO/HSE/GAR/BDP/2010.3 [Internet]. Scientific review of variola virus research, 1999-2010. Available at: http://www.who.int/csr/resources/publications/WHO_HSE_GAR_BDP_2010_3/ru/.

2. Taub DD, Ershler WB, Janowski M et al. Immunity from smallpox vaccine persists for decades: a longitudinal study. Am J Med. 2008; 121 (12):1058-64. doi: 10.1016/j.amjmed.2008.08.019.

3. Verardi PH, Titong A, Hagen CJ. A vaccinia virus renaissance: new vaccine and immunotherapeutic uses after smallpox eradication. Hum Vaccin Immunother.2012; 8 (7): 961-70. doi: 10.4161/hv.21080.

4. Volz A, Sutter G. Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development. Adv Virus Res. 2017; 97:187 -243. doi: 10.1016/bs.aivir.2016.07.001.

5. Maksyutov RA, Yakubitskyi SN, Kolosova IV, et al. Comparing New-Generation Candidate Vaccines against Human Orthopoxvirus Infections. Acta Naturae. 2017; 9 (2): 88-93.

6. Springer YP, Hsu CH, Werle ZR, et al. Orthopoxvirus Infection in an Alaska Resident. Clin Infect Dis. 2017; 64 (12): 1737-1741. doi: 10.1093/cid/cix219.

7. Orr N, Forman M, Marcus H, et al. Clinical and immune responses after revaccination of israeli adults with the Lister strain of vaccinia virus. The Journal of Infectious Diseases. 2004; 190: 1295-302.

8. Kennedy RB, Poland GA, Ovsyannikova IG, et al. Impaired innate, humoral, and cellular immunity despite a take in smallpox vaccine recipients. Vaccine. 2016; 34 (28): 3283-90.

9. Reif DM, Motsinger-Reif AA, McKinney B.A et al. integrated analysis of genetic and proteomic data identifies biomarkers associated with adverse events following smallpox vaccination. genes immun. 2009;10(2):112-9.

10. Yudin NS, Igoshin AV, Lutova S.L et al. Association between polymorphisms in genes encoding 2'-5'-oligoadenylate synthetases and the humoral immune response upon vaccination against tick-borne encephalitis. Vavilov Journal of Genetics and Breeding. 2018; 22 (4): 445-451 (In Russ).

11. Medunitsyn NV. Vaccinology. Moscow; 2004 (In Russ).

12. Ermilova OS, Gin'ko ZI, Belyavskaya VA, et al. Analysis of Vaccinal Process Peculiarities in Persons Immunized with Smallpox Live Vaccine in Case of Primary Vaccination and Revaccination. Problems of Particularly Dangerous Infections. 2015; (1): 75-78 (In Russ).

13. Zachs L. Statistical Evaluation. Moscow: Statistica; 1976 (In Russ).

14. Marennikova SS., Shchelkunov SN. Orthopoxviruses pathogenic to humans. Moscow: KMKScientific Press Ltd. 1998 (In Russ).

15. Leendertz SAJ, Stern D, Theophil D et al. A cross-sectional serosurvey of anti-orthopoxvirus antibodies in Central and Western Africa. Viruses. 2017; 29; 9 (10). pii: E278. doi: 10.3390/v9100278.

16. Bhatia A, Sekhon HK, Kaur G. Sex hormones and immune dimorphism. Scientific World Journal. 2014:159150. doi: 10.1155/2014/159150.

17. Troy JD, Hill HR, Ewell MG et al. Sex difference in immune response to vaccination: а participant-level meta-analysis of randomized trials of IMVAMUNE smallpox vaccine. Vaccine. 2015,33 (41): 5425-31. doi: 10.1016/j.vaccine.2015.08.032.