After a century when aluminium salts have been the only vaccine adjuvants approved for human use, the field of adjuvants has become one of the fastest growing disciplines in immunology and vaccine development. The scope of this book is to review the state-of-the-art of development of novel adjuvants and the science that supports them.
Immunological adjuvants are substances that are added to vaccine formulations to increase their efficacy. Adjuvants can increase the magnitude and duration of the immune response induced by vaccination and allow for antigen sparing. In addition, adjuvants can modulate the quality of the adaptive immunity favoring protective cellular and humoral responses, such as viral neutralization, bacterial opsonization and killing of infected cells. Finally, adjuvants can increase the breadth of protection of vaccines directed against pathogens, such as influenza, that are characterized by antigen variability or that circulate in different strains or clades.
There is an increasing need of novel adjuvants for preventive vaccines targeting infectious diseases for which conventional formulations have failed. New adjuvants are also needed to improve existing vaccines in the elderly, infants and chronically infected subjects that mount a suboptimal immune response. In addition, adjuvants could be very useful for the development of effective therapeutic vaccines against chronic infections and cancer. This book gives an overview of vaccine adjuvants with a special focus on their composition and mechanism of action.
The rationales for including adjuvants in subunit vaccine formulations are described by Schijns and Lavelle in Chapter 1. The authors highlight the ability of adjuvants to dictate the quality of the immune response to the coadministered antigen and propose that different vaccines may require a diverse adjuvant depending on the correlate of protection.
Despite the strong impact of adjuvants on vaccine efficacy, only few adjuvanted vaccines are licensed for human use. The first adjuvant to be licensed worldwide is alum, which has been used in several pediatric vaccine formulations for the last 70 years. In Chapter 2, Mutwiri and coworkers describe alum composition and mechanism of action. Several decades after the introduction of alum, other particulate adjuvants, called virosomes and oil-in-water emulsions, have been licensed in Europe to increase the immunogenicity of influenza vaccines. These adjuvants are described in great detail in Chapters 3 and 4. Special attention was dedicated to the squalene-based oil-in-water emulsions (MF59, AS03 and AF03) that were largely used to improve the efficacy of the vaccines against the recent H1N1 pandemic influenza outbreak and that are also licenses for the avian H5N1 prepandemic vaccines. In the last few years, the knowledge of the human innate immune system has rapidly progressed leading to the identification of a novel class of receptors called Toll-like receptors (TLRs), which are validated targets for the development of new immunomodulators. The TLR4 agonist monophosphoryl lipid A adsorbed to alum has been recently licensed for a human papillomavirus vaccine in Europe and USA (Chapters 2 and 6). Although no other TLR agonist has been licensed as human vaccine adjuvant, many have been extensively studied in preclinical and clinical studies, among them the TLR9 agonist CpG oligonucleotides (Chapter 9) and small molecules of the imidazoquinoline class targeting TLR7 and 8 (Chapter 7). The CD8 T cell cytotoxic response has been traditionally associated to protection against intracellular pathogens and cancer. However, subunit vaccines generally induce very poor CD8 responses. Ragupathi and coworkers in Chapter 5 describe the structure and the clinical applications in cancer vaccine trials of an adjuvant of the saponin class called QS21, which is able to induce CD8 responses when formulated with subunit vaccines. In the last chapter of this book Schijns and Lavelle describe the future trends in adjuvant discovery. Interestingly, they suggest that in the future TLR agonists or novel immunepotentiators targeting alternative receptors (e.g., C-type lectins, Rig-I and Nod-like receptors) may be combined with novel synthetic antigen delivery systems, such as biodegradable nanoparticles. These novel formulations would allow for co-delivery of antigen and immunopotentiator to the same antigen-presenting cell, greatly enhancing the final adjuvant effect.
