As editors Gabain and Klade state in the preface to this book, their aim was to give an overview and insight into the rational approach to vaccine discovery, design and development. To accomplish this goal, they sought state-of-the-art contributions from leading experts within academia, biotechnology, the vaccine industry and a regulatory agency. The intended audience would be comprised of persons not yet highly specialized in the arena of vaccine research and product development, but who seek a broad perspective of several aspects of the field as presented in the 11 chapters.
Chapter 1 by Alkan on ‘The immunological fundamentals’ is particularly valuable. This is a must-read for new scientists entering the vaccine research field, as the chapter navigates the complex field of vaccine immunobiology with the right mix of overview and sufficient detail so as to not overwhelm the reader. The discussion of innate immunity, Toll-like receptors, Nod-like receptors and new innate cells provides clarity to this area of immunology to provide basic insights to the adjuvants in development discussed later in the book. The sections on adaptive immunity are also excellent as the interplay with innate immunity is explained, as well as the process of generation of immune memory, generation of diversity of the adaptive response, and T-cell and B-cell functions and interactions. Differences between the adult and infant immune response are not addressed.
Nearly all vaccines currently in use in humans were developed through a traditional empiric approach. A new era of vaccine discovery occurred with the application of multigenome analysis and genomic DNA-based screening approaches to identify potential vaccine candidates. In chapter 2, Grandi and Nagy review the theory and application of reverse vaccinology and the antigenome technologies that have been applied in recent years to identify potential vaccine ingredients. The reader learns how both methods rely on in silico prediction of human antibody responses and compliment each other in the identification of potential vaccine antigens.
Adjuvants are valuable and often necessary components of vaccines to enhance immunogenicity. For decades, it was thought that aluminum salts, the most frequently used adjuvant in humans, produced an immune-enhancing response by facilitating the formation of a depot of vaccine at the injection site. In chapter 3, Fox et al. explain the many specific mechanisms of alum as an adjuvant, including the newly discovered role of stimulation of the Nalp3 inflammasome (explained in chapter 1). The use of emulsions as newer adjuvants is reviewed allowing a clearer understanding of the composition and mechanism of effectiveness for MF59 (in use by Novartis vaccines), ASO2, ASO3 and ASO4 (in use by GlaxoSmithKline vaccines) and others. Taking advantage of our newer understanding of Toll-like receptors and Nod-like receptors (discussed in chapter 1), modern adjuvant constructs seek to direct the immune response by preferentially activating the signaling cascades of specific innate immunity receptors.
In chapter 4 by Flyer and Butler, the issue of alternative vaccine delivery by a proprietary skin patch developed by the company where they work called Intercell USA, Inc. is addressed. No mention is made of oral administration. Safe use of needles has become an increasing issue since the rise in incidence of AIDS and hepatitis C. In developing countries, reuse of needles and syringes is somewhat commonplace, so an alternative to vaccine delivery by injection is of ongoing interest.
Chapter 5 by Loessner et al. is titled ‘Employing live microbes for vaccine delivery’, which includes discussion of live, attenuated vaccines (LAVs), tumor-targeting bacteria, recombinant antiviral subunit vaccines, recombinant viral vectors, attenuated vaccinia virus vaccines, avipoxviruses, measles viruses, yellow fever virus, adenoviruses, viral-like particles and other viral vector systems, as well as the topic of the title. There are three licensed bacterial LAVs: bacillus Calmette–Guérin, Salmonella typhi strain Ty21a and Vibrio cholera strain CVD 103-HgR. Next-generation bacterial LAVs include a Salmonella LAV under study by this group. Issues of level and timing of antigen expression, expression cassettes and antigen release are presented. One section of this chapter presents research on using LAVs as vectors for delivery of nucleic acid vaccines, and delivery of tumor vaccines and adjuvant molecules. This chapter especially is extensively referenced.
Microbial systems have been used for more than a decade to produce viral and bacterial antigens as components of licensed vaccines including yeast species (e.g., Saccharomyces cerevisiae for hepatitis B vaccine). Chapter 6 by Wacker and Casimiro presents information on synthesizing vaccines with microbes. There is greater depth to the discussion of an Escherichia coli expression platform and glycoconjugate vaccines under development by the company that the authors work for – GlycoVaxyn.
A rare glimpse into the nuts and bolts of vaccine manufacturing complexities is offered in chapter 7 by Schlegl and Hahn. Vaccines are a broad class of biomolecules including polysaccharides, proteins, viral particles, attenuated viral and bacterial strains, and whole cells of killed microbes. How a vaccine manufacturer proceeds with various separation methods (centrifugation, membrane separation and precipitation), and chromatography methods and purification steps is described with several illustrations.
Chapters 8 and 9 share the same title: ‘Cutting-edge approaches toward novel and cross-protective influenza vaccines’. Arnon and Ben-Yedidia discuss peptide- and epitope-based influenza vaccine development as novel approaches to circumvent the annual strain selections mandated by hemagglutinin and neuraminidase antigenic drift. Recent research has been directed towards identifying common, cross-reactive antigenic constituents of the influenza virus, so as to elicit broad cross protection across strains. Roose et al. review the principles for deconstructing the hemagglutinin antigen and evaluating the M2 protein as a possible new immunogen against this ubiquitous virus.
Chapter 10 by Dubischar-Kastner et al. presents an overview of the development programs of the human papilloma virus vaccine Gardasil® (Merck & Co., Inc.), and a traveler’s vaccine against Japanese encephalitis virus. The authors take the reader through the clinical Phase I, II and III steps toward licensure and the postmarketing promises that the companies who developed the vaccines needed to make to gain approval. The portfolio of studies provided to regulatory agencies to receive approval for the proposed indications are presented, allowing the reader to gain an insight into the impressive effort and enormous expense required today to bring a novel vaccine to market.
Pfleiderer writes the final chapter 11 entitiled: ‘The bumpy road toward vaccine registration: how to overcome regulatory hurdles’. The author provides his perspective on the topic, developed by experience along ‘the bumpy road’. The advice on overcoming regulatory hurdles is necessarily vague since the regulations are continuously changing as information evolves scientifically. I was hoping for an enlightening reference list, but alas, there was none since this area of development of novel vaccines continues to have a shade of mystery to the process.
Overall, all of the chapters are well written. References are generally excellent, thorough and up-to-date through 2011. The index is lacking in detail, making the book more of a one-time read rather than a reference source. The book’s first seven chapters are more strongly tied to the intended audience.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.