New‐Generation Vaccine Adjuvants

Abstract

The currently available vaccines represent an outstanding success story in modern medicine, as they are responsible for a huge reduction in morbidity and mortality worldwide. However, it is clear that new approaches are necessary to enable the development of vaccines against more difficult pathogens, which are not yet under control, including human immunodeficiency virus (HIV), malaria and Methicillin‐resistant Staphylococcal aureus (MRSA). In addition, vaccines are necessary to counter emerging pathogen threats such as pandemic influenza and Ebola viruses. Potential improvements to current vaccines may include the addition of new adjuvants, which are able to induce more potent immune responses, more rapid responses or responses with an expanded breadth of pathogen coverage. New‐generation adjuvants are now becoming available which may enable the development of new and improved vaccines, and this is currently a very active area of research and development.

Key Concepts

  • Vaccines are safe and effective and have had a major impact on reducing the impact of infectious diseases in the twentieth century and continue to do so early in the twenty‐first century.
  • Adjuvants are included in vaccines to increase the immune response to the vaccine antigens.
  • Vaccine adjuvants are often necessary to enable vaccines to be effective.
  • Most currently available childhood vaccines contain insoluble aluminium salts as adjuvants.
  • To enable the development of vaccines against some more difficult pathogens, such as HIV and malaria, more potent adjuvants will be required.
  • New‐generation adjuvants normally comprise several components combined together to achieve the best immune response to the vaccine.
  • New vaccine adjuvants will have to undergo extensive safety testing before they will ever be included in licensed vaccines.
  • Recently, it was identified that traditional small molecular weight drugs could perform as adjuvants, opening up the possibility of discovering many more new adjuvant‐active compounds.
  • Formulation science is a key contributor to allow the development of safe and effective vaccine adjuvants.
  • It is becoming increasingly important to fully understand the mechanism of action of vaccine adjuvants, how they work is important.

Keywords: vaccines; vaccine adjuvants; infectious diseases; enhanced immunity

Figure 1. The composition of new‐generation vaccines. Increasingly, new‐generation vaccines will comprise highly purified 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 on immune cells.
Figure 2. The mechanism of action of MF59 adjuvant, which is included in an approved influenza vaccine (Fluad™). Following intramuscular injection, MF59 and flu vaccine 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 and respond by secreting chemical messages called chemokines, which are responsible for recruiting further monocytes and immune cells from the circulation into the site of injection. Activated macrophages, which contain flu antigens and MF59, migrate to the draining lymph nodes. MF59 uptake also enhances monocyte differentiation into dendritic cells, a very potent APC. APCs then migrate from the tissues to the lymph nodes, where they present flu vaccine antigens to T cells, resulting in activation. The T cells in turn contribute to activation of specific B cells, which are responsible for secreting antibodies. The antibodies then move into the blood circulation and offer protection against influenza infection.
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Further Reading

De Gregorio E and Rappuoli R (2014) From empiricism to rational design: a personal perspective of the evolution of vaccine development. Nature Reviews Immunology 14 (7): 505–514.

Hogenesch H (2013) Mechanism of immunopotentiation and safety of aluminum adjuvants. Frontiers in Immunology 3: 406.

Levine MM , Dougan G , Good MF , et al. (2010) New Generation Vaccines, 4th edn. New York: Informa Healthcare.

O'Hagan DT (ed) (2000) Vaccine Adjuvants; Preparation Methods and Research Protocols. New Jersey: Humana Press.

O'Hagan DT , Ott GS , Nest GV , et al. (2013) The history of MF59(®) adjuvant: a phoenix that arose from the ashes. Expert Review of Vaccines 12 (1): 13–30.

Rappuoli R , Mandl CW , Black S and De Gregorio E (2011) Vaccines for the twenty‐first century society. Nature Reviews Immunology 11 (12): 865–872.

Rappuoli R , Pizza M , Del Giudice G and De Gregorio E (2014) Vaccines, new opportunities for a new society. Proceedings of the National Academy of Sciences of the United States of America 111 (34): 12288–12293.

Schijns VEJC and O'Hagan DT (2006) Immunopotentiators in Modern Vaccines. Amsterdam; Boston: Elsevier Academic Press.

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How to Cite close
O'Hagan, Derek T(Jul 2015) New‐Generation Vaccine Adjuvants. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020177.pub2]