Abstract
Adjuvants constitute a critical component in vaccine development in terms of both stimulating and directing immune responses of a suitable profile to promote protection against a diverse range of disease targets. In the past, the field of adjuvant research was mainly dominated by empirical testing and serendipity. However, there is a strong need to develop new generations of adjuvants based on rational design, as well as a requirement to characterise and comprehend their mechanism(s) of action. Adjuvant development can be characterised as an iterative process where potential candidates are repeatedly tested in vitro and in vivo for immunogenicity and optimised in terms of formulation and delivery. Novel lead candidates of adjuvants with a suitable immunological profile relative to specific disease targets are subsequently selected and evaluated in efficacy studies. A central aspect in such a development and selection process is to determine the adjuvant activity on T-cell function in vivo. Expanding our knowledge on these mechanisms will improve our chance of developing new successful vaccines designed to target specific diseases.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J. M., Hoffmann, J. A. (1996) The dorsoventral regulatory gene cassette spatzle/toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86, 973–983.
Medzhitov, R., PrestonHurlburt, P., Janeway, C. A. (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394–397.
Hargreaves, D. C., Medzhitov, R. (2005) Innate sensors of microbial infection. J Clin Immunol 25, 503–510.
Garcon, N., Chomez, P., Van Mechelen, M. (2007) GlaxoSmithKline Adjuvant systems in vaccines: concepts, achievements and perspectives. Expert Rev Vaccines 6, 723–739.
Mosca, F., Tritto, E., Muzzi, A., Monaci, E., Bagnoli, F., Iavarone, C., et al. (2008) Molecular and cellular signatures of human vaccine adjuvants. Proc Natl Acad Sci USA 105, 10501–10506.
Seubert, A., Monaci, E., Pizza, M., O’Hagan, D. T., Wack, A. (2008) The adjuvants aluminum hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells. J Immunol 180, 5402–5412.
Schellack, C., Prinz, K., Egyed, A., Fritz, J. H., Wittmann, B., Ginzler, M., et al. (2006) IC31, a novel adjuvant signaling via TLR9, induces potent cellular and humoral immune responses. Vaccine 24, 5461–5472.
Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., et al. (2008) Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 9, 847–856.
Korsholm, K. S., Agger, E. M., Foged, C., Christensen, D., Dietrich, J., Andersen, C. S., et al. (2007) The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes. Immunology 121, 216–226.
Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A., Coffman, R. L. (1986) Two types of murine helper T cell clone. 1. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136, 2348–2357.
Harrington, L. E., Hatton, R. D., Mangan, P. R., Turner, H., Murphy, T. L., Murphy, K. M., et al. (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6, 1123–1132.
Lyons, A. B., Parish, C. R. (1994) Determination of lymphocyte division by flow-cytometry. J Immunol Methods 171, 131–137.
Seder, R. A., Darrah, P. A., Roederer, M. (2008) T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol 8, 247–258.
Gauduin, M. C., Kaur, A., Ahmad, S., Yilma, T., Lifson, J. D., Johnson, R. P. (2004) Optimization of intracellular cytokine staining for the quantitation of antigen-specific CD4+ T cell responses in rhesus macaques. J Immunol Methods 288, 61–79.
Horton, H., Thomas, E. P., Stucky, J. A., Frank, I., Moodie, Z., Huang, Y. D., et al. (2007) Optimization and validation of an 8-color intracellular cytokine staining (ICS) assay to quantify antigen-specific T cells induced by vaccination. J Immunol Methods 323, 39–54.
Acknowledgments
Linda Christensen and Maria Nørtoft Sørensen are acknowledged for their excellent technical assistance. We are indebted to all colleagues, present and former, at the Department of Infectious Disease Immunology for input to the described protocols.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Lindenstrøm, T., Andersen, P., Agger, E.M. (2010). Determining Adjuvant Activity on T-Cell Function In Vivo: Th Cells. In: Davies, G. (eds) Vaccine Adjuvants. Methods in Molecular Biology, vol 626. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-585-9_15
Download citation
DOI: https://doi.org/10.1007/978-1-60761-585-9_15
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60761-584-2
Online ISBN: 978-1-60761-585-9
eBook Packages: Springer Protocols