Abstract
Anthrax is an acute infectious disease caused by Bacillus anthracis. We previously reported that the adjuvant CIA06B, which consists of TLR4 agonist CIA05 and aluminum hydroxide (alum), enhanced the immune response to anthrax protective antigen (PA) in mice. This study was carried out to determine whether CIA06B can enhance long-term immune responses to PA in mice. BALB/c mice were immunized intramuscularly three times at 2-week intervals with recombinant PA alone or PA combined with alum or CIA06B. At 8 and 24 weeks post-immunization, the immunological responses including serum anti-PA IgG antibody titer, toxin-neutralizing antibody titer, splenic cytokine secretion and the frequency of PA-specific memory B cells were assessed. Compared with mice injected with PA alone or PA plus alum, mice injected with PA plus CIA06B had higher titers of serum anti-PA IgG antibodies, and higher frequencies of PA-specific memory B cells and interferon-γ secreting cells. Furthermore, anti-PA antibodies induced by CIA06B were more effective in neutralizing anthrax toxin. These results demonstrated that CIA06B is capable of providing long-term immunity when used as an adjuvant in a PA-based anthrax vaccine.
Similar content being viewed by others
References
Bernasconi, N.L., E. Traggiai, and A. Lanzavecchia. 2002. Maintenance of serological memory by polyclonal activation of human memory B cells. Science 298: 2199–2202.
Brey, R.N. 2005. Molecular basis for improved anthrax vaccines. Advanced Drug Delivery Reviews 57: 1266–1292.
Cho, Y.J., B.Y. Ahn, N.G. Lee, D.H. Lee, and D.S. Kim. 2006. A combination of E. coli DNA fragments and modified lipopolysaccharides as a cancer immunotherapy. Vaccine 24: 5862–5871.
Crotty, S., and R. Ahmed. 2004. Immunological memory in humans. Seminars in Immunology 16: 197–203.
Cybulski, R.J., Jr., P. Sanz, and A.D. O’Brien. 2009. Anthrax vaccination strategies. Molecular Aspects of Medicine 30: 490–502.
Friedlander, A.M., and S.F. Little. 2009. Advances in the development of next-generation anthrax vaccines. Vaccine 27(Suppl 4): D28–D32.
Han, J.E., H.K. Kim, S.A. Park, S.J. Lee, H.J. Kim, G.H. Son, Y.T. Kim, Y.J. Cho, and N.G. Lee. 2010. A nontoxic derivative of lipopolysaccharide increases immune responses to Gardasil HPV vaccine in mice. International Immunopharmacology 10: 169–176.
Han, J.E., S.R. Wui, S.A. Park, N.G. Lee, K.S. Kim, Y.J. Cho, and H.J. Kim. 2012. Comparison of the immune responses to the CIA06-adjuvanted human papillomavirus L1 VLP vaccine with those against the licensed HPV vaccine Cervarix in mice. Vaccine 30: 4127–4134.
Lee, C.H., and C.M. Tsai. 1999. Quantification of bacterial lipopolysaccharides by the purpald assay: measuring formaldehyde generated from 2-keto-3-deoxyoctonate and heptose at the inner core by periodate oxidation. Analytical Biochemistry 267: 161–168.
Little, S.F., B.E. Ivins, P.F. Fellows, M.L. Pitt, S.L. Norris, and G.P. Andrews. 2004. Defining a serological correlate of protection in rabbits for a recombinant anthrax vaccine. Vaccine 22: 422–430.
Mock, M., and A. Fouet. 2001. Anthrax. Annual Review of Microbiology 55: 647–671.
Ochsenbein, A.F., D.D. Pinschewer, S. Sierro, E. Horvath, H. Hengartner, and R.M. Zinkernagel. 2000. Protective long-term antibody memory by antigen-driven and T help-dependent differentiation of long-lived memory B cells to short-lived plasma cells independent of secondary lymphoid organs. Proceedings of the National Academy of Sciences of the USA 97: 13263–13268.
Peachman, K.K., M. Rao, C.R. Alving, R. Burge, S.H. Leppla, V.B. Rao, and G.R. Matyas. 2006. Correlation between lethal toxin-neutralizing antibody titers and protection from intranasal challenge with Bacillus anthracis Ames strain spores in mice after transcutaneous immunization with recombinant anthrax protective antigen. Infection and Immunity 74: 794–797.
Pezard, C., P. Berche, and M. Mock. 1991. Contribution of individual toxin components to virulence of Bacillus anthracis. Infection and Immunity 59: 3472–3477.
Pittman, P.R., G. Kim-Ahn, D.Y. Pifat, K. Coonan, P. Gibbs, S. Little, J.G. Pace-Templeton, R. Myers, G.W. Parker, and A.M. Friedlander. 2002. Anthrax vaccine: immunogenicity and safety of a dose-reduction, route-change comparison study in humans. Vaccine 20: 1412–1420.
Reuveny, S., M.D. White, Y.Y. Adar, Y. Kafri, Z. Altboum, Y. Gozes, D. Kobiler, A. Shafferman, and B. Velan. 2001. Search for correlates of protective immunity conferred by anthrax vaccine. Infection and Immunity 69: 2888–2893.
Rhie, G.E., Y.M. Park, J.H. Chun, C.K. Yoo, W.K. Seong, and H.B. Oh. 2005. Expression and secretion of the protective antigen of Bacillus anthracis in Bacillus brevis. FEMS Immunology and Medical Microbiology 45: 331–339.
Sallusto, F., A. Lanzavecchia, K. Araki, and R. Ahmed. 2010. From vaccines to memory and back. Immunity 33: 451–463.
Slifka, M.K., and R. Ahmed. 1998. Long-lived plasma cells: a mechanism for maintaining persistent antibody production. Current Opinion in Immunology 10: 252–258.
Tross, D., and D.M. Klinman. 2008. Effect of CpG oligonucleotides on vaccine-induced B cell memory. Journal of Immunology 181: 5785–5790.
Turnbull, P.C. 2000. Current status of immunization against anthrax: old vaccines may be here to stay for a while. Current Opinion in Infectious Diseases 13: 113–120.
Unwin, C., N. Blatchley, W. Coker, S. Ferry, M. Hotopf, L. Hull, K. Ismail, I. Palmer, A. David, and S. Wessely. 1999. Health of UK servicemen who served in Persian Gulf War. Lancet 353: 169–178.
Wui, S.R., H.K. Kim, J.E. Han, J.M. Kim, Y.H. Kim, J.H. Chun, Y.J. Cho, and N.G. Lee. 2011. A combination of the TLR4 agonist CIA05 and alum promotes the immune responses to Bacillus anthracis protective antigen in mice. International Immunopharmacology 11: 1195–1204.
Acknowledgments
This study was supported by a grant from Korea Centers for Disease Control and Prevention, a grant of the TEPIK, Korea Healthcare technology R&D Project by Ministry of Health & Welfare, Republic of Korea (A103001), and a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (No. 20090236).
Conflict of interest
NG Lee: Inventor of EyeGene-owned patents, Research Grant (EyeGene).
Ethics
All animal experiments were conducted using protocols approved by the animal care and use committees at Sejong University (Document no.: SJ-20100401007 approved on April 19, 2010).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wui, S.R., Han, J.E., Kim, Y.H. et al. Increased long-term immunity to Bacillus anthracis protective antigen in mice immunized with a CIA06B-adjuvanted anthrax vaccine. Arch. Pharm. Res. 36, 464–471 (2013). https://doi.org/10.1007/s12272-013-0034-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-013-0034-5