New Generation Vaccine Adjuvants

Derek T O'Hagan, Novartis Vaccines and Diagnostics, Inc., Siena, Italy

Published online: April 2007

DOI: 10.1002/9780470015902.a0020177

Vaccines represent an outstanding success story in modern medicine and are responsible for a huge reduction in morbidity and mortality worldwide, but it is clear that improvements are necessary to enable the development of successful vaccines against some difficult pathogens, including human immunodeficiency virus (HIV), hepatitis C virus (HCV) and respiratory syncytial virus (RSV). Vaccine improvements may include the addition of new adjuvants, which are able to induce higher immune responses, or immune responses with greater breadth, to cover the broad antigenic diversity of some pathogens. New generation adjuvants are starting to become available which may enable the development of new generation vaccines.

Keywords: vaccines; vaccine adjuvants; vaccine delivery; infectious diseases; immune responses

Figure 1. The optimal composition of new generation vaccines. Increasingly, new-generation vaccines will comprise recombinant protein antigens, synthetic immune potentiators, designed to stimulate only the appropriate immune response required for protective immunity and a delivery system, which will physically link the antigens to the immune potentiators and will focus their effects only to the relevant immune cells.
Figure 2. Summary of the mechanism of action of MF59 adjuvant. Following injection of Fluad™ through a syringe and needle into the muscle, MF59 and flu vaccine antigens are taken up by phagocytic cells. These include macrophages which differentiate from blood monocytes and can act as antigen presenting cells (APCs) for T cells. Monocytes and other cell types are activated by the uptake of MF59 adjuvant and respond by secreting chemical messages called chemokines, which are responsible for recruiting further monocytes and additional immune cells from the circulation into the site of injection. Activated macrophages, which contain flu antigens and MF59 adjuvant migrate towards the draining lymph nodes. MF59 uptake also enhances monocyte differentiation into dendritic cells, a type of APC that is very potent at presenting antigens. These APCs also migrate from the tissues to the lymph nodes, where they present flu vaccine antigens to naive T cells, resulting in activation of these cells. While macrophages are thought to act only as APCs for T cells that have previously been stimulated, dendritic cells express high levels of costimulatory molecules which confer upon them the special ability to activate T cells that have not previously encountered the antigen. The flu-specific T cells contribute to further activation of the flu-specific B cells, which are responsible for secreting flu-specific antibodies, which move into the blood circulation and offer protection against influenza infection and disease. MF59 directly enhances the number of flu antigen-specific T cells activated and also results in the secretion of higher levels of flu-specific antibodies into the blood. Reproduced by permission of Derek O'Hagan.
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 Further Reading
    book Glueck R (2004) "Immunostimulating reconstituted influenza virosomes". In: Levine MM, Kaper JB, Rappuoli R, Liu MA and Good MF (eds) New Generation Vaccines, 3rd edn, chap. 25, pp. 295–304. New York: Marcel Dekker
    book O'Hagan DT (ed.) (2000) Vaccine Adjuvants; Preparation Methods and Research Protocols. New Jersey: Humana Press.
    book O'Hagan DT (2004) "New developments in vaccine delivery systems". In: Levine MM, Kaper JB, Rappuoli R, Liu MA and Good MF (eds) New Generation Vaccines, 3rd edn, chap. 22, pp. 259–270. New York: Marcel Dekker
    O'Hagan DT and Rappuoli R (2006) Novel approaches to pediatric vaccine delivery. Advanced Drug Delivery Reviews 58(1): 29–51.
    book Kenney RT and Edelman R (2004) "Adjuvants for the future". In: Levine MM, Kaper JB, Rappuoli R, Liu MA and Good MF (eds) New Generation Vaccines, 3rd edn, chap. 18, pp. 213–224. New York: Marcel Dekker
    Klinman DE (2006) Adjuvant activity of CpG oligodeoxynucleotides. International Reviews of Immunology 25(3–4): 135–154.
    Lindblad EB (2004) Aluminium adjuvants–in retrospect and prospect. Vaccine 22(27–28): 3658–3668.
    book Podda A and Del Giudice G (2004) "MF59 adjuvant emulsion".In: Levine MM, Kaper JB, Rappuoli R, Liu MA and Good MF (eds) New Generation Vaccines, 3rd edn, chap. 19, pp. 225–236. New York: Marcel Dekker
    book Schijns VEJC and O'Hagan DT (eds.) (2005) Immunopotentiators in Modern Vaccines. Amsterdam: Academic Press.

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Article Title: New Generation Vaccine Adjuvants
 
How to Cite close
O'Hagan, Derek T(Apr 2007) New Generation Vaccine Adjuvants. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020177]