Back
 AiM  Vol.6 No.3 , March 2016
Polyfunctional T Cell and Neutralizing Antibody Responses to ACAM2000TM Smallpox Vaccine Immunization in Primary-Vaccinated Individuals
Abstract: Smallpox eradication was successful via prophylactic administration of live attenuated vaccinia virus. As a result of the discontinuation of the smallpox immunization program, many individuals are now susceptible to smallpox virus infection should it be used as a biological weapon. Presently, only individuals at high risk for exposure are required to receive smallpox vaccine, such as laboratory personnel that handle variola/vaccinia virus. This study endeavored to investigate a one-year period of vaccinia virus-specific T cell responses using polychromatic flow cytometry and neutralizing (Nt) antibody responses using plaque reduction neutralization test (PRNT) in individuals receiving primary immunization (n = 5) with ACAM2000TM smallpox vaccine. Functional and phenotypic profiles of vaccinia virus-specific T cell responses were characterized. Each single functional measurement {CD107a/b expression, production of interferon g (IFN-g), macrophage inflammatory protein 1b (MIP-1b), interleukin 2 (IL-2), and tumor necrosis factor a (TNF-a)} demonstrated that vaccinia virus-specific CD8+ T cells were functional at least one time point after vaccination (p ≤ 0.05). However, vaccinia virus-specific CD4+ T cells were functional only for MIP-1b production (p ≤ 0.05). Vaccinia virus-specific CD8+ T cells induced in these individuals showed increased polyfunctionality in at least 2 phenotypes relative to pre-vaccination (p ≤ 0.05). Although only three of five individuals (60%) showed positive Nt antibody (titer ≥ 20) at first month after vaccination, all five individuals (100%) demonstrated Nt antibody at 2 months, post-immunization. Interestingly, all vaccinees could retain the Nt antibody for 6 months after primary vaccination. In conclusion, ACAM2000TM smallpox vaccine induced both polyfunctional T cell-and Nt antibody-responses in primary immunized individuals.
Cite this paper: Sukhumvittaya, S. , Ampol, S. , Pattanapanyasat, K. and Kantakamalakul, W. (2016) Polyfunctional T Cell and Neutralizing Antibody Responses to ACAM2000TM Smallpox Vaccine Immunization in Primary-Vaccinated Individuals. Advances in Microbiology, 6, 169-177. doi: 10.4236/aim.2016.63017.
References

[1]   Puissant, B. and Combadière, B. (2006) Keeping the Memory of Smallpox Virus. Cellular and Molecular Life Sciences, 63, 2249-2259.
http://dx.doi.org/10.1007/s00018-006-6313-2

[2]   Monath, T.P., Caldwell, J.R., Mundt, W., Fusco, J., Johnson, C.S., Buller, M., et al. (2004) ACAM2000 Clonal Vero Cell Culture Vaccinia Virus (New York City Board of Health strain)—A Second-Generation Smallpox Vaccine for Biological Defense. International Journal of Infectious Diseases, 8S2, S31-S44.

[3]   Kennedy, R.B., Ovsyannikova, I.G., Jacobson, R.M. and Poland, G.A. (2009) The Immunology of Smallpox Vaccine. Current Opinion in Immunology, 21, 314-320.
http://dx.doi.org/10.1016/j.coi.2009.04.004

[4]   Moss, B. (2011) Smallpox Vaccines: Targets of Protective Immunity. Immunological Reviews, 239, 8-16.
http://dx.doi.org/10.1111/j.1600-065X.2010.00975.x

[5]   Harrington, L.E., Most, R., Whitton, J.L. and Ahmed, R. (2002) Recombinant Vaccinia Virus-Induced T-Cell Immunity: Quantitation of the Response to the Virus Vector and the Foreign Epitope. Journal of Virology, 76, 3329-3337.
http://dx.doi.org/10.1128/JVI.76.7.3329-3337.2002

[6]   Taub, D.D., Ershler, W.B., Janowski, M., Artz, A., Keys, M.L., McKelveya, J., et al. (2008) Immunity from Smallpox Vaccine Persists for Decades: A Longitudinal Study. American Journal of Medicine, 121, 1058-1064.
http://dx.doi.org/10.1016/j.amjmed.2008.08.019

[7]   Precopio, M.L., Betts, M.R., Parrino, J., Price, D.A., Gostick, E., Ambrozak, D.R., et al. (2007) Immunization with Vaccinia Virus Induces Polyfunctional and Phenotypically Distinctive CD8+ T Cell Responses. Journal of Experimental Medicine, 204, 1405-1416.
http://dx.doi.org/10.1084/jem.20062363

[8]   Cox, J.H. (1999) HIV-1-Specific Cytotoxic T-Cell Assays. In: Michael, N.L. and Kim, J.H., Eds., Methods in Molecular Medicine, Vol. 17: HIV Protocols, Humana Press, Totowa, 355-371.
http://dx.doi.org/10.1385/0-89603-369-4:355

[9]   Newman, F.K., Frey, S.E., Blevins, T.P., Mandava, M., Bonifacio, A., Yan, L., et al. (2003) Improved Assay to Detect Neutralizing Antibody Following Vaccination with Diluted or Undiluted Vaccinia (Dryvax) Vaccine. Journal of Clinical Microbiology, 41, 3154-3157.
http://dx.doi.org/10.1128/JCM.41.7.3154-3157.2003

[10]   Fenner, F., Henderson, D.A., Arita, I., Jezek, Z. and Ladnyi, I.D. (1988) Smallpox and Its Eradication. World Health Organization, Geneva.

[11]   Nalca, A. and Zumbrun, E.E. (2010) ACAM2000: The New Smallpox Vaccine for United States Strategic National Stockpile. Drug Design, Development and Therapy, 4, 71-79.
http://dx.doi.org/10.2147/DDDT.S3687

[12]   Watson, J.C. and Peter, G. (1999) General Immunization Practices. In: Plotkin, S.A. and Orenstein, W.A., Eds., Vaccines, 3rd Edition, WB Saunders Company, Philadelphia, 47-73.

[13]   Hammarlund, E., Lewis, M.W., Hansen, S.G., Strelow, L.I., Nelson, J.A., Sexton, G.J., et al. (2003) Duration of Antiviral Immunity after Smallpox Vaccination. Nature Medicine, 9, 1131-1137.
http://dx.doi.org/10.1038/nm917

[14]   Basu, R.N., Jezek, Z. and Ward, N.A. (1979) Smallpox and Its Eradication from the South-East Asia Region. WHO/ SEARO, 36, 1-3.

[15]   Rock, M.T., Yoder, S.M., Wright, P.F., Talbot, T.R., Edwards, K.M. and Crowe Jr., J.E. (2005) Differential Regulation of Granzyme and Perforin in Effector and Memory T Cells Following Smallpox Immunization. Journal of Immunology, 174, 3757-3764.
http://dx.doi.org/10.4049/jimmunol.174.6.3757

[16]   Amanna, I.J., Slifka, M.K. and Crotty, S. (2006) Immunity and Immunological Memory Following Smallpox Vaccination. Immunological Reviews, 211, 320-337.
http://dx.doi.org/10.1111/j.0105-2896.2006.00392.x

[17]   Mack, T.M., Noble Jr., J. and Thomas, D.B. (1972) A Prospective Study of Serum Antibody and Protection against Smallpox. The American Journal of Tropical Medicine and Hygiene, 21, 214-218.

[18]   Sarkar, J.K., Mitra, A.C. and Mukherjee, M.K. (1975) The Minimum Protective Level of Antibodies in Smallpox. Bulletin of the World Health Organization, 52, 307-311.

[19]   Artenstein, A.W., Iohnson, C., Marbury, T.C., Morrison, D., Blum, P.S., Kemp, T., et al. (2005) A Novel, Cell Culture-Derived Smallpox Vaccine in Vaccinia Naive Adults. Vaccine, 23, 3301-3309.
http://dx.doi.org/10.1016/j.vaccine.2005.01.079

[20]   Frey, S.E., Newman, F.K., Kennedy, J.S., Ennis, F., Abate, G., Hoft, D.F., et al. (2009) Comparison of the Safety and Immunogenicity of ACAM1000 and ACAM2000 and Dryvax in Healthy Vaccinia Naive Adults. Vaccine, 27, 1637-1644.
http://dx.doi.org/10.1016/j.vaccine.2008.11.079

[21]   Walsh, S.R., Wilck, M.B., Dominguez, D.J., Zablowsky, E., Bajimaya, S., Gagne, L.S., et al. (2013) Safety and Immunogenicity of Modified Vaccinia Ankara in Hematopoietic Stem Cell Transplant Recipients: A Randomized, Controlled Trial. The Journal of Infectious Diseases, 207, 1888-1897.
http://dx.doi.org/10.1093/infdis/jit105

[22]   Kennedy, R.B., Ovsyannikova, I.G., Pankratz, V.S., Vierkant, R.A., Jacobson, R.M., Ryan, M.A., et al. (2009) Gender Effects on Humoral Immune Responses to Smallpox Vaccine. Vaccine, 27, 3319-3323.
http://dx.doi.org/10.1016/j.vaccine.2009.01.086

[23]   Troy, J.D., Hill, H.R., Ewell, M.G. and Frey, S.E. (2015) Sex Difference in Immune Response to Vaccination: A Participant-Level Meta-Analysis of Randomized Trials of IMVAMUNE® Smallpox Vaccine. Vaccine, 33, 5425-5431.
http://dx.doi.org/10.1016/j.vaccine.2015.08.032

 
 
Top